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  1. Article ; Online: Metabolome Analysis Reveals Excessive Glycolysis via PI3K/AKT/mTOR and RAS/MAPK Signaling in Methotrexate-Resistant Primary CNS Lymphoma-Derived Cells.

    Takashima, Yasuo / Hayano, Azusa / Yamanaka, Ryuya

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 26, Issue 11, Page(s) 2754–2766

    Abstract: Purpose: Metabolome analysis is an emerging method that provides insight into intracellular and physiologic responses. Methotrexate (MTX) is an antifolate that suppresses DNA syntheses by inhibiting dihydrofolate reductase. High-dose methotrexate ... ...

    Abstract Purpose: Metabolome analysis is an emerging method that provides insight into intracellular and physiologic responses. Methotrexate (MTX) is an antifolate that suppresses DNA syntheses by inhibiting dihydrofolate reductase. High-dose methotrexate treatment with deferred radiotherapy is a standard protocol in primary central nervous system lymphoma (PCNSL) treatments. However, most cases come to relapse-acquired resistance, in which the role of metabolic pathways is largely unknown.
    Experimental design: Metabolome analysis in methotrexate-resistant PCNSL-derived cells (designated as TK-MTX and HKBML-MTX) was performed to detect alternative metabolites and pathways.
    Results: The metabolomic analyses using capillary electrophoresis-time-of-flight mass spectrometry detected 188 and 169 peaks in TK- and HKBML-derived cells, respectively, including suppression of central carbon metabolism, lipid metabolism, nucleic acid metabolism, urea cycle, branched chain and aromatic amino acids, and coenzyme metabolism. Particularly, whole suppressive metabolic pathways were demonstrated in TK-MTX, whereas HKBML-MTX indicated partially enhanced pathways of the urea cycle, amino acid metabolism, and coenzyme metabolism. Reciprocally detected metabolites for glycolysis, including induced glucose and reduced glycogen, and induced lactate and reduced pyruvate, in addition to increased lactate dehydrogenase activity, which is involved in Warburg effect. Thereby, ATP was increased in both methotrexate-resistant PCNSL-derived cells. Furthermore, we specifically found that PI3K/AKT/mTOR and RAS/MAPK signaling pathways were activated in TK-MTX but not in HKBML-MTX by growth rate with inhibitors and gene expression analysis, suggestive of cell type-specific methotrexate-resistant metabolic pathways.
    Conclusions: These results can help us understand targeted therapies with selective anticancer drugs in recurrent CNS lymphoma-acquired resistance against methotrexate.
    MeSH term(s) Animals ; Antimetabolites, Antineoplastic/pharmacology ; Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Proliferation ; Central Nervous System Neoplasms/drug therapy ; Central Nervous System Neoplasms/genetics ; Central Nervous System Neoplasms/metabolism ; Central Nervous System Neoplasms/pathology ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic/drug effects ; Glycolysis ; Humans ; Lymphoma/drug therapy ; Lymphoma/genetics ; Lymphoma/metabolism ; Lymphoma/pathology ; Metabolome/drug effects ; Methotrexate/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mitogen-Activated Protein Kinases/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; ras Proteins/genetics ; ras Proteins/metabolism
    Chemical Substances Antimetabolites, Antineoplastic ; Biomarkers, Tumor ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; ras Proteins (EC 3.6.5.2) ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2020-02-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-18-3851
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    Zs.A 4223: Show issues Location:
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  2. Article ; Online: Reciprocal expression of the immune response genes CXCR3 and IFI44L as module hubs are associated with patient survivals in primary central nervous system lymphoma.

    Takashima, Yasuo / Hamano, Momoko / Yoshii, Kengo / Hayano, Azusa / Fukai, Junya / Iwadate, Yasuo / Kajiwara, Koji / Hondoh, Hiroaki / Yamanaka, Ryuya

    International journal of clinical oncology

    2023  Volume 28, Issue 3, Page(s) 468–481

    Abstract: Purpose: Here, we investigated expression modules reflecting the reciprocal expression of the cancer microenvironment and immune response-related genes associated with poor prognosis in primary central nervous system lymphoma (PCNSL).: Methods: ... ...

    Abstract Purpose: Here, we investigated expression modules reflecting the reciprocal expression of the cancer microenvironment and immune response-related genes associated with poor prognosis in primary central nervous system lymphoma (PCNSL).
    Methods: Weighted gene coexpression network analysis revealed representative modules, including neurogenesis, immune response, anti-virus, microenvironment, gene expression and translation, extracellular matrix, morphogenesis, and cell adhesion in the transcriptome data of 31 PCNSL samples. RESULTS : Gene expression networks were also reflected by protein-protein interaction networks. In particular, some of the hub genes were highly expressed in patients with PCNSL with prognoses as follows: AQP4, SLC1A3, GFAP, CXCL9, CXCL10, GBP2, IFI6, OAS2, IFIT3, DCN, LRP1, and LUM with good prognosis; and STAT1, IFITM3, GZMB, ISG15, LY6E, TGFB1, PLAUR, MMP4, FTH1, PLAU, CSF3R, FGR, POSTN, CCR7, TAS1R3, small ribosomal subunit genes, and collagen type 1/3/4/6 genes with poor prognosis. Furthermore, prognosis prediction formulae were constructed using the Cox proportional-hazards regression model, which demonstrated that the IP-10 receptor gene CXCR3 and type I interferon-induced protein gene IFI44L could predict patient survival in PCNSL.
    Conclusion: These results indicate that the differential expression and balance of immune response and microenvironment genes may be required for PCNSL tumor growth or prognosis prediction, which would help understanding the mechanism of tumorigenesis and potential therapeutic targets in PCNSL.
    MeSH term(s) Humans ; Central Nervous System Neoplasms/genetics ; Central Nervous System Neoplasms/pathology ; Proportional Hazards Models ; Lymphoma/genetics ; Immunity ; Central Nervous System/metabolism ; Central Nervous System/pathology ; Prognosis ; Tumor Microenvironment/genetics ; Membrane Proteins/metabolism ; RNA-Binding Proteins ; Receptors, CXCR3/metabolism
    Chemical Substances IFITM3 protein, human ; Membrane Proteins ; RNA-Binding Proteins ; CXCR3 protein, human ; Receptors, CXCR3
    Language English
    Publishing date 2023-01-06
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1400227-9
    ISSN 1437-7772 ; 1341-9625
    ISSN (online) 1437-7772
    ISSN 1341-9625
    DOI 10.1007/s10147-022-02285-8
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    Zs.A 4828: Show issues Location:
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  3. Article ; Online: Radiation-Induced Schwannomas and Neurofibromas: A Systematic Review.

    Yamanaka, Ryuya / Hayano, Azusa

    World neurosurgery

    2017  Volume 104, Page(s) 713–722

    Abstract: Objective: Radiation-induced benign peripheral nerve sheath tumors are uncommon late complications of irradiation. We conducted the largest systematic review of individual patient data.: Methods: We performed a systematic search of PubMed databases ... ...

    Abstract Objective: Radiation-induced benign peripheral nerve sheath tumors are uncommon late complications of irradiation. We conducted the largest systematic review of individual patient data.
    Methods: We performed a systematic search of PubMed databases and compiled a comprehensive literature review. Kaplan-Meier analysis was used to investigate survival, and statistical significance was assessed with a log-rank test.
    Results: We analyzed 40 cases of radiation-induced benign peripheral nerve sheath tumors. The histologic distributions were 28 schwannomas, 11 neurofibromas, and 1 ganglioneuroma. The average age of radiation exposure for development of primary lesions was 14.9 ± 15.5 years, and the latency period between radiotherapy to the onset of secondary tumors was 24.5 ± 12.7 years. The average irradiation dose delivered was 26.3 ± 20.3 Gy. The median overall survival for all cases was not reached (95% confidence interval, 22-not reached) months, with 10-year survival rates of 65.2%. Surgical negative margin was a positive prognostic factor for radiation-induced benign peripheral nerve sheath tumors.
    Conclusions: The risk of incidence of secondary benign peripheral nerve sheath tumors in patients treated with radiotherapy should be considered in long-term follow-up periods. At present, complete surgical resection is the main stay for the treatment of radiation-induced benign peripheral nerve sheath tumors.
    MeSH term(s) Adolescent ; Adult ; Child ; Child, Preschool ; Cross-Sectional Studies ; Ganglioneuroma/etiology ; Ganglioneuroma/mortality ; Humans ; Infant ; Infant, Newborn ; Kaplan-Meier Estimate ; Neoplasms, Radiation-Induced/etiology ; Neoplasms, Radiation-Induced/mortality ; Neoplasms, Second Primary/etiology ; Neoplasms, Second Primary/mortality ; Nerve Sheath Neoplasms/etiology ; Nerve Sheath Neoplasms/mortality ; Neurilemmoma/etiology ; Neurilemmoma/mortality ; Neurofibroma/etiology ; Neurofibroma/mortality ; Radiotherapy Dosage ; Risk Factors ; Young Adult
    Language English
    Publishing date 2017-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2534351-8
    ISSN 1878-8769 ; 1878-8750
    ISSN (online) 1878-8769
    ISSN 1878-8750
    DOI 10.1016/j.wneu.2017.05.066
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    Zs.A 1159: Show issues Location:
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  4. Article ; Online: Radiation-Induced Sarcomas of the Central Nervous System: A Systematic Review.

    Yamanaka, Ryuya / Hayano, Azusa

    World neurosurgery

    2017  Volume 98, Page(s) 818–828.e7

    Abstract: Objective: Radiation-induced sarcomas (RISs) of the central nervous system are an uncommon late risk of irradiation. We conducted a systematic review of individual patient data to characterize RISs.: Methods: We conducted a systemic search of the ... ...

    Abstract Objective: Radiation-induced sarcomas (RISs) of the central nervous system are an uncommon late risk of irradiation. We conducted a systematic review of individual patient data to characterize RISs.
    Methods: We conducted a systemic search of the PubMed databases and compiled a comprehensive literature review. Student t tests were used to evaluate differences between variables. Kaplan-Meier analysis was used to estimate survival. Statistical significance was assessed using a log-rank test.
    Results: We analyzed 180 cases of RISs, including 59 osteosarcomas, 50 fibrosarcomas, and 16 malignant fibrous histiocytomas. The average age of onset for primary lesions was 28.8 ± 17.9 years, and the average dose of radiation delivered to the primary lesion was 51.4 ± 18.6 Gy. The latency period between radiotherapy and the onset of sarcomas was 12.4 ± 8.6 years. The median overall survival time for all sarcoma patients was 11 months, with a 5-year survival rate of 14.3%. The median survival in patients who received chemotherapy was 18 months, with a 2-year survival rate of 39.4%, whereas patients who did not receive chemotherapy had a median survival of 5 months and a 2-year survival rate of 13.7% (P < 0.0001).
    Conclusions: The risk of secondary sarcomas in patients treated with cranial radiotherapy warrants longer follow-up periods beyond the standard time frame typically designated for determining the risk of primary tumor relapse. Moreover, chemotherapy should be considered a potential treatment option for RISs.
    MeSH term(s) Adult ; Age of Onset ; Brain Neoplasms/radiotherapy ; Central Nervous System Neoplasms/etiology ; Central Nervous System Neoplasms/mortality ; Humans ; Kaplan-Meier Estimate ; Neoplasms, Radiation-Induced/etiology ; Neoplasms, Radiation-Induced/mortality ; Neoplasms, Radiation-Induced/therapy ; Radiotherapy/adverse effects ; Sarcoma/etiology ; Sarcoma/mortality ; Sarcoma/therapy ; Time Factors ; Treatment Outcome ; Young Adult
    Language English
    Publishing date 2017-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2534351-8
    ISSN 1878-8769 ; 1878-8750
    ISSN (online) 1878-8769
    ISSN 1878-8750
    DOI 10.1016/j.wneu.2016.11.008
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  5. Article ; Online: Radiation-Induced Malignant Peripheral Nerve Sheath Tumors: A Systematic Review.

    Yamanaka, Ryuya / Hayano, Azusa

    World neurosurgery

    2017  Volume 105, Page(s) 961–970.e8

    Abstract: Objective: Radiation-induced malignant peripheral nerve sheath tumors (MPNSTs) are an uncommon late risk of irradiation. We conducted the largest systematic review to date of individual patient data for patients with these tumors.: Methods: We ... ...

    Abstract Objective: Radiation-induced malignant peripheral nerve sheath tumors (MPNSTs) are an uncommon late risk of irradiation. We conducted the largest systematic review to date of individual patient data for patients with these tumors.
    Methods: We conducted a systematic search using the PubMed database, and compiled a systematic literature review. We used Kaplan-Meier analysis and a log-rank test to estimate survival.
    Results: We analyzed 65 radiation-induced and 26 radiation-associated MPNSTs in patients with neurofibromatosis. The mean ages of onset for primary lesions of the 2 types were 31.7 ± 18.2 and 17.1 ± 12.4 years, respectively (P = 0.0008). The latency periods between radiotherapy and onset of the 2 types of MPNSTs were 13.5 ± 7.8 and 11.8 ± 7.5 years, respectively (P = 0.3101). The median overall survival and 5-year survival were 11 months (6.8%) and 23 months (5.8%), respectively (P = 0.2168). Negative surgical margin and patient sex were variables retained for the prognosis of radiation-induced and radiation-associated MPNSTs.
    Conclusions: The prognosis of radiation-induced and radiation-associated MPNST was worse than that reported for de novo MPNSTs. Surgical complete resection is the mainstay for treatment of radiation-induced and radiation-associated MPNSTs. The risk of incidence of secondary MPNSTs in patients treated with radiotherapy warrants longer follow-up periods.
    MeSH term(s) Databases, Factual/statistics & numerical data ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Meta-Analysis as Topic ; Neoplasms, Radiation-Induced/etiology ; Neoplasms, Radiation-Induced/mortality ; Neurilemmoma/etiology ; Neurilemmoma/mortality ; Radiotherapy/adverse effects
    Language English
    Publishing date 2017-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2534351-8
    ISSN 1878-8769 ; 1878-8750
    ISSN (online) 1878-8769
    ISSN 1878-8750
    DOI 10.1016/j.wneu.2017.06.010
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  6. Article ; Online: Secondary Craniofacial Sarcomas Following Retinoblastoma: A Systematic Review.

    Yamanaka, Ryuya / Hayano, Azusa

    World neurosurgery

    2017  Volume 101, Page(s) 722–730.e4

    Abstract: Objective: We conducted the largest systematic review of individual patient data to characterize secondary craniofacial sarcomas following retinoblastoma.: Methods: We conducted a systemic search of the PubMed databases and compiled a comprehensive ... ...

    Abstract Objective: We conducted the largest systematic review of individual patient data to characterize secondary craniofacial sarcomas following retinoblastoma.
    Methods: We conducted a systemic search of the PubMed databases and compiled a comprehensive literature review. Student t tests were used to evaluate differences between variables. Kaplan-Meier analysis was used to estimate survival. Statistical significance was assessed using a log-rank test.
    Results: We analyzed 220 cases of secondary craniofacial sarcomas, including 112 osteosarcomas. The average age (±SD) of onset for retinoblastoma was 1.20 ± 2.77 years. External-beam radiotherapy was delivered in 207 patients (94.0%) and chemotherapy was delivered in 53 patients (24.0%) patients. The latency period between retinoblastoma diagnosis and the onset of secondary sarcomas was 12 years. Cranial extension was found in 66 patients (30.0%). The median overall survival was worse with cranial extension (P = 0.0073). In cranial extended patients, the median survival in patients who received chemotherapy was 41 months, whereas patients who did not receive chemotherapy had a median survival of 12 months (P = 0.0020).
    Conclusions: The risk of incidence of secondary sarcomas in retinoblastoma patients warrants longer follow-up periods. Moreover, chemotherapy should be considered as a potential treatment option for secondary cranial sarcomas following retinoblastoma.
    MeSH term(s) Bone Neoplasms/diagnosis ; Bone Neoplasms/mortality ; Facial Bones/pathology ; Humans ; Neoplasms, Second Primary/diagnosis ; Neoplasms, Second Primary/mortality ; Osteosarcoma/diagnosis ; Osteosarcoma/mortality ; Retinoblastoma/diagnosis ; Retinoblastoma/mortality ; Sarcoma/diagnosis ; Sarcoma/mortality ; Skull Neoplasms/diagnosis ; Skull Neoplasms/mortality ; Survival Rate/trends
    Language English
    Publishing date 2017-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2534351-8
    ISSN 1878-8769 ; 1878-8750
    ISSN (online) 1878-8769
    ISSN 1878-8750
    DOI 10.1016/j.wneu.2017.02.031
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  7. Article ; Online: CD276 and the gene signature composed of GATA3 and LGALS3 enable prognosis prediction of glioblastoma multiforme.

    Takashima, Yasuo / Kawaguchi, Atsushi / Hayano, Azusa / Yamanaka, Ryuya

    PloS one

    2019  Volume 14, Issue 5, Page(s) e0216825

    Abstract: Glioma is the most common type of primary brain tumor, accounting for 40% of malignant brain tumors. Although a single gene may not be a marker, an expression profiling and multivariate analyses for cancer immunotherapy must estimate survival of patients. ...

    Abstract Glioma is the most common type of primary brain tumor, accounting for 40% of malignant brain tumors. Although a single gene may not be a marker, an expression profiling and multivariate analyses for cancer immunotherapy must estimate survival of patients. In this study, we conducted expression profiling of immunotherapy-related genes, including those in Th1/2 helper T and regulatory T cells, and stimulatory and inhibitory checkpoint molecules associated with survival prediction in 571 patients with malignant and aggressive form of gliomas, glioblastoma multiforme (GBM). Expression profiling and Random forests analysis of 21 immunosuppressive genes and Kaplan-Meier analysis in 158 patients in the training data set suggested that CD276, also known as B7-H3, could be a single gene marker candidate. Furthermore, prognosis prediction formulas, composed of Th2 cell-related GATA transcription factor 3 (GATA3) and immunosuppressive galactose-specific lectin 3 (LGALS3), based on 67 immunotherapy-related genes showed poor survival with high scores in training data set, which was also validated in another 413 patients in the test data set. The CD276 expression helped distinguish survival curves in the test data set. In addition, inhibitory checkpoint genes, including T cell immunoreceptor with Ig and ITIM domains, V-set domain containing T cell activation inhibitor 1, T-cell immunoglobulin and mucin-domain containing 3, and tumor necrosis factor receptor superfamily 14, showed potential as secondary marker candidates. These results suggest that CD276 expression and the gene signature composed of GATA3 and LGALS3 are effective for prognosis in GBM and will help us understanding target pathways for immunotherapy in GBM.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; B7 Antigens/biosynthesis ; Biomarkers, Tumor/biosynthesis ; Brain Neoplasms/metabolism ; Brain Neoplasms/mortality ; Brain Neoplasms/pathology ; Disease-Free Survival ; Female ; GATA3 Transcription Factor/biosynthesis ; Galectin 3/biosynthesis ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Glioblastoma/mortality ; Glioblastoma/pathology ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Proteins/biosynthesis ; Survival Rate
    Chemical Substances B7 Antigens ; Biomarkers, Tumor ; CD276 protein, human ; GATA3 Transcription Factor ; GATA3 protein, human ; Galectin 3 ; LGALS3 protein, human ; Neoplasm Proteins
    Language English
    Publishing date 2019-05-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0216825
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  8. Article ; Online: Cell-type-specific sensitivity of bortezomib in the methotrexate-resistant primary central nervous system lymphoma cells.

    Hayano, Azusa / Takashima, Yasuo / Yamanaka, Ryuya

    International journal of clinical oncology

    2019  Volume 24, Issue 9, Page(s) 1020–1029

    Abstract: Background: Methotrexate (MTX) is used in first-line treatment of primary central nervous system lymphoma (PCNSL), but most cases result in relapse-acquired resistance to MTX. However, only few studies have reported on internal changes and ... ...

    Abstract Background: Methotrexate (MTX) is used in first-line treatment of primary central nervous system lymphoma (PCNSL), but most cases result in relapse-acquired resistance to MTX. However, only few studies have reported on internal changes and chemotherapies in PCNSL.
    Methods: In this study, we generated two MTX-resistant PCNSL cell lines, designated MTX-HKBML and MTX-TK, in addition to a MTX-resistant Burkitt lymphoma cell line, designated MTX-RAJI. We examined gene expression changes and drug sensitivity to a proteasome inhibitor, bortezomib, in these cells.
    Results: Cytotoxic tests revealed that the 50% inhibitory concentration for MTX in MTX-HKBML is markedly higher than that in the other two cell lines. Expression of the genes in MTX and folate metabolisms, including gamma-glutamyl hydrolase and dihydrofolate reductase, are upregulated in both MTX-HKBML and MTX-TK, whereas the gene expression of folylpolyglutamate synthetase, thymidylate synthase, and methylenetetrahydrofolate dehydrogenase 1 were upregulated and downregulated in MTX-HKBML and MTX-TK, respectively, on the other hand, bortezomib sensitivity was observed in MTX-TK, as compared with control TK, but not in MTX-HKBML.
    Conclusion: These results indicate the cell-type-specific changes downstream of metabolic pathways for MTX and folate, bortezomib sensitivity, and purine and pyrimidine syntheses, in each PCNSL cell line. The MTX-resistant lymphoma cell lines established may be useful for in vitro relapse models for MTX and development of salvage chemotherapy and drug discovery.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Bortezomib/administration & dosage ; Bortezomib/pharmacology ; Cell Line, Tumor ; Central Nervous System Neoplasms/drug therapy ; Central Nervous System Neoplasms/genetics ; Central Nervous System Neoplasms/pathology ; Drug Resistance, Neoplasm/drug effects ; Folic Acid/genetics ; Folic Acid/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lymphoma/drug therapy ; Lymphoma/genetics ; Lymphoma/pathology ; Lymphoma, Non-Hodgkin/drug therapy ; Lymphoma, Non-Hodgkin/pathology ; Methotrexate/administration & dosage ; Methotrexate/pharmacology ; Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics ; Minor Histocompatibility Antigens/genetics ; Molecular Targeted Therapy ; Peptide Synthases/genetics ; Thymidylate Synthase/genetics
    Chemical Substances Minor Histocompatibility Antigens ; Bortezomib (69G8BD63PP) ; Folic Acid (935E97BOY8) ; MTHFD1 protein, human (EC 1.5.1.5) ; Methylenetetrahydrofolate Dehydrogenase (NADP) (EC 1.5.1.5) ; Thymidylate Synthase (EC 2.1.1.45) ; Peptide Synthases (EC 6.3.2.-) ; folylpolyglutamate synthetase (EC 6.3.2.17) ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2019-04-16
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1400227-9
    ISSN 1437-7772 ; 1341-9625
    ISSN (online) 1437-7772
    ISSN 1341-9625
    DOI 10.1007/s10147-019-01451-9
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  9. Article ; Online: Secondary glioma following acute lymphocytic leukemia: therapeutic implications.

    Yamanaka, Ryuya / Hayano, Azusa

    Neurosurgical review

    2016  Volume 40, Issue 4, Page(s) 549–557

    Abstract: We conducted a comprehensive review of the literature to characterize the etiology of secondary glioma following acute lymphocytic leukemia (ALL) patients. The analysis included 98 cases with an average age of onset of ALL of 5.9 years (range 1.5 to 26). ...

    Abstract We conducted a comprehensive review of the literature to characterize the etiology of secondary glioma following acute lymphocytic leukemia (ALL) patients. The analysis included 98 cases with an average age of onset of ALL of 5.9 years (range 1.5 to 26). The average latency period was 7.8 years until diagnosis of secondary glioma. Radiation therapy was administered in 92 cases for the primary malignancy at an average dose of 20.7 Gy. The median survival time of patients treated with multimodality treatment for secondary glioma was 23 months (95 % confidence interval 12-27 months), and multimodality therapy improved survival time significantly (p = 0.0029). The exact cause for the development of glioma following ALL is not clear. The risk of a secondary glioma in childhood cancer survivors may be influenced by genetic and other predisposing factors as well as by treatment type. In patients diagnosed with ALL, the risk of secondary glioma warrants a longer follow-up period that continues long after the risk of relapse of the primary malignancy has passed. Moreover, multimodality therapy should be considered in cases of secondary glioma following ALL.
    MeSH term(s) Adolescent ; Adult ; Brain Neoplasms/diagnosis ; Brain Neoplasms/etiology ; Brain Neoplasms/therapy ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Glioma/diagnosis ; Glioma/etiology ; Glioma/therapy ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Young Adult
    Language English
    Publishing date 2016-05-10
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 6907-3
    ISSN 1437-2320 ; 0344-5607
    ISSN (online) 1437-2320
    ISSN 0344-5607
    DOI 10.1007/s10143-016-0733-8
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  10. Article: Experiences and expectations for glioma immunotherapeutic approaches.

    Yamanaka, Ryuya / Hayano, Azusa

    Frontiers in oncology

    2014  Volume 4, Page(s) 355

    Language English
    Publishing date 2014-12-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2014.00355
    Database MEDical Literature Analysis and Retrieval System OnLINE

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