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  • 1
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    Participation of CD11b and F4/80 Molecules in the Conjunctival Eosinophilia of Experimental Allergic Conjunctivitis
    S. Karger AG ; 2010
    In:  International Archives of Allergy and Immunology Vol. 151, No. 2 ( 2010), p. 129-136
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 151, No. 2 ( 2010), p. 129-136
    Abstract: 〈 i 〉 Background: 〈 /i 〉 CD11b and F4/80 are macrophage surface markers. How these molecules participate in allergic eosinophil infiltration remains unclear. We examined the roles CD11b and F4/80 play in the conjunctival eosinophil infiltration associated with experimental allergic conjunctivitis. 〈 i 〉 Methods: 〈 /i 〉 Ragweed-immunized BALB/c mice were challenged with ragweed in eye drops to induce conjunctival eosinophil infiltration. The effect of challenge on conjunctival CD11b+ and F4/80+ cell numbers was determined by immunohistochemistry. In the same model, blocking anti-CD11b and anti-F4/80 Abs were injected intraperitoneally during the induction or the effector phase, or subconjunctivally 2 h before challenge, to determine their effect on challenge-induced conjunctival eosinophilia. To examine whether eosinophils express CD11b and F4/80 molecules, splenocytes from IL-5 gene-electroporated mice were subjected to flow cytometric analysis. To clarify the involvement of CD11b and F4/80 in conjunctival eosinophil infiltration, mice were intraperitoneally injected with anti-CD11b and anti-F4/80 Abs and then subconjunctivally injected with eotaxin to induce conjunctival eosinophilia. 〈 i 〉 Results: 〈 /i 〉 Ragweed challenge elevated conjunctival CD11b+ and F4/80+ cell numbers. Systemic anti-CD11b and anti-F4/80 Ab treatments during the effector phase, but not in either the induction phase or the local injection of Ab, suppressed conjunctival eosinophil infiltration in ragweed-induced conjunctivitis. Most splenic eosinophils from IL-5 gene-introduced mice expressed CD11b and F4/80. Systemic anti-CD11b and anti-F4/80 Ab treatment suppressed conjunctival eosinophilia induced by subconjunctival eotaxin injection. 〈 i 〉 Conclusions: 〈 /i 〉 CD11b and F4/80 appear to participate in conjunctival eosinophil infiltration in allergic conjunctivitis. Their involvement in conjunctival eosinophilia appears to be due to their expression on eosinophils rather than on macrophages.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000236002
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2010
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  • 2
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    Induction of hTERT expression and phosphorylation by estrogen via Akt cascade in human ovarian cancer cell lines
    Springer Science and Business Media LLC ; 2004
    In:  Oncogene Vol. 23, No. 26 ( 2004-06-03), p. 4505-4515
    Details
    In: Oncogene, Springer Science and Business Media LLC, Vol. 23, No. 26 ( 2004-06-03), p. 4505-4515
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    URL: Article
    DOI: 10.1038/sj.onc.1207582
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2004
    detail.hit.zdb_id: 2008404-3
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  • 3
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    Multiple Myeloma Oncogene 1 (MUM1)/Interferon Regulatory Factor 4 (IRF4) Upregulates Monokine Induced by Interferon-gamma (MIG) Gene Expression in B-Cell Malignancy.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 1111-1111
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1111-1111
    Abstract: MUM1(multiple myeloma oncogene 1)/IRF4(interferon regulatory factor 4) is a transcription regulatory factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas/leukemias and has been reported to predict an unfavorable outcome in some lymphoma subtypes including diffuse large B-cell lymphoma (DLBCL) and B-cell chronic lymphocytic leukemia (B-CLL). To elucidate its role in B-cell malignancies, we prepared stably MUM1-expressing Ba/F3 cells, which proliferated at a higher rate than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3 (FKBP3), the Monokine induced by interferon-gamma (MIG), Fas apoptotic inhibitory molecule (Faim) and Zinc finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1 in inducible MUM1 expressing system. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed in chromatin immunoprecipitation assay. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and its receptor CXCR3 was also coexpressed in B-CLL cell lines that were positive for MUM1. Interestingly, treatment with neutralizing antibodies against MIG and its receptor, CXCR3, partially inhibited the proliferation of two MUM1-expressing B-CLL cell lines. These results suggest that MUM1 plays certain roles in the progression of B-cell lymphomas/leukemias by regulating the expression of various genes including MIG.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.1111.1111
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 4
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    Association of a Haplotype (196Phe/532Ser) in the Interleukin-1-Receptor-Associated Kinase (IRAK1) Gene With Low Radial Bone Mineral Density in Two Independent Populations
    Wiley ; 2003
    In:  Journal of Bone and Mineral Research Vol. 18, No. 3 ( 2003-03-01), p. 419-423
    Details
    In: Journal of Bone and Mineral Research, Wiley, Vol. 18, No. 3 ( 2003-03-01), p. 419-423
    Type of Medium: Online Resource
    ISSN: 0884-0431
    URL: Article
    DOI: 10.1359/jbmr.2003.18.3.419
    RVK:
    XA 52230
    Language: English
    Publisher: Wiley
    Publication Date: 2003
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  • 5
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    DS-3201, a Potent EZH1/2 Dual Inhibitor, Demonstrates Antitumor Activity Against Non-Hodgkin Lymphoma (NHL) Regardless of EZH2 Mutation
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2217-2217
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2217-2217
    Abstract: Enhancer of zests homologous (EZH)1 and its close homolog EZH2 are component of polycomb repressive complex (PRC) 2 protein complex, and play redundant and crucial role for the maintenance of transcriptional repression by tri-methylating histone H3 lysine 27 (H3K27). Hyper tri-methylation of H3K27 has been associated with lymphoma and myeloma progression, suggesting that PRC2 is a therapeutic target for hematological malignancies. Selective EZH2 inhibitors induce compensatory activation of EZH1 which in turn re-activates PRC2 function. We hypothesized that dual inhibition of EZH1 and EZH2 is more effective than selective EZH2 inhibition as anti-tumor therapy. We have developed a novel EZH1 and EZH2 dual inhibitor DS-3201, which simultaneously inhibited the enzymatic activity of EZH1 and EZH2 in nano-molar concentration. DS-3201 showed anti-proliferative effect against various NHL cells, such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and peripheral T-cell lymphoma, with GI50 values less than 100 nM regardless of EZH2 gain-of-function mutations. DS-3201 also induced differentiation of undifferentiated NHL cells with increment of cell lineage specific markers and which induced cell death in vitro. DS-3201 also showed synergistic effect with the standard of care agents for NHL in vitro and in vivo. An open-label phase 1 clinical study was initiated to examine the safety and pharmacokinetics of multiple-dose monotherapy of DS-3201b which is the salt form of DS-3201 in patients with NHL (ClinicalTrials.gov Identifier: NCT02732275). Eighteen patients with relapsed or refractory NHL were enrolled. The patients received oral administration of DS-3201b once daily in a 28-day cycle at dose of 150, 200 and 300 mg. Preliminary efficacy results (D. Maruyama, et al. ASH 2017), showed that the overall response rate was 58.8% (10/17) with 1 complete response and 9 partial responses (PR). Thirteen NHL patients including five follicular lymphoma (FL) and one DLBCL were analyzed for gene mutation status by targeted gene sequencing. EZH2 mutation was detected only in one FL patient, who achieved PR. It was suggested that DS-3201b has clinical activity against NHL, regardless of the mutation status of EZH2. Disclosures Honma: Daiichi Sankyo: Employment. Nosaka:Daiichi Sankyo: Employment. Shiroishi:Daiichi Sankyo: Employment. Takata:Daiichi Sankyo: Employment. Hama:Daiichi Sankyo: Employment. Yamamoto:Daiichi Sankyo RD Novare: Employment. Adachi:Daiichi Sankyo: Employment. Maruyama:Mundipharma International: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Dai-ichi-Sankyo: Honoraria; Bristol-Myers Squibb: Honoraria; Biomedis International: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Fujifilm: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Dai-Nippon-Sumitomo: Honoraria; Asahi Kasei Pharma: Honoraria; AstraZeneca: Research Funding; Solasia Pharma: Research Funding; Pfizer: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Novartis: Research Funding; Otsuka: Research Funding; Amgen Astellas BioPharma: Research Funding; Astellas Pharma: Research Funding; Abbvie: Research Funding; GlaxoSmithKline: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding. Tobinai:Chugai Pharma: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Eisai: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; SERVIER: Research Funding; Abbvie: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Zenyaku Kogyo: Consultancy, Honoraria; HUYA Bioscience International: Consultancy, Honoraria. Ishida:Kyowa Hakko Kirin Co.Ltd: Honoraria, Research Funding; Celgene K.K: Honoraria, Research Funding; Bayer AG: Research Funding; Mundiparma K: Honoraria. Kusumoto:Bristol-Myers Squibb: Honoraria, Research Funding; Chugai Pharmaceutical Co. Ltd: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding. Tsukasaki:Daiich-Sankyo: Consultancy; Ono Pharma: Consultancy; HUYA: Consultancy, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Research Funding; Celgene: Honoraria; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Fujioka:Daiichi Sankyo: Employment. Watanabe:Daiichi Sankyo: Employment. Kanno:Daiichi Sankyo: Employment. Kumazawa:Daiichi Sankyo RD Novare: Employment. Fujitani:Daiichi Sankyo: Employment. Araki:Daiichi Sankyo: Employment. Fujiwara:Daiichi Sankyo: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-99-113379
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 6
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    Association of Molecular Variants, Haplotypes, and Linkage Disequilibrium Within the Human Vitamin D‐Binding Protein ( DBP ) Gene With Postmenopausal Bone Mineral Density
    Wiley ; 2003
    In:  Journal of Bone and Mineral Research Vol. 18, No. 9 ( 2003-09), p. 1642-1649
    Details
    In: Journal of Bone and Mineral Research, Wiley, Vol. 18, No. 9 ( 2003-09), p. 1642-1649
    Abstract: Possible contribution of vitamin D‐binding protein ( DBP ) gene for determination of BMD was tested by characterizing 13 SNPs in 384 adult Japanese women. When the effect of a specific single SNP was tested, five SNPs (−39C 〉 T, IVS1+827C 〉 T, IVS1+1916C 〉 T, IVS1‐1154A 〉 G, and IVS11+1097G 〉 C) correlated with BMD significantly at various levels. The chromosomal dosage of one haplotype (T‐C‐C‐G‐T‐C in −39C 〉 T, IVS1+827C 〉 T, IVS1+1916C 〉 T, IVS1‐1154A 〉 G, D432E, and IVS11+1097G 〉 C) displayed significant correlation with adjusted radial BMD ( r = 0.15, p = 0.008; n = 331). Multiple regression analyses revealed a most significant correlation with the combination of IVS1+827C 〉 T and D432E ( r 2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. Introduction: Osteoporosis results from the interplay of multiple environmental and genetic determinants. The gene encoding vitamin D‐binding protein ( DBP ), a key factor for regulating calcium homeostasis through the vitamin D endocrine system, is a probable candidate for conferring susceptibility to osteoporosis. Methods: To test a possible contribution of the DBP gene for determination of bone mineral density (BMD) of adult women, we have characterized 13 single nucleotide polymorphisms (SNPs) within the DBP gene in DNA from 384 adult Japanese women and attempted to correlate specific SNPs with BMD. Results and Conclusions: Sixteen major haplotypes accounted for 80% of the variations, indicating allelic complexity in this genomic region. Pairwise linkage disequilibrium (LD), measured by the D ′ and r 2 statistics, demonstrated a general pattern of decline with increasing distance, but individual LD values within small genomic segments were diverse. Regression analysis for adjusted BMD revealed significant correlation with respect to five of them (−39C 〉 T, IVS1+827C 〉 T, IVS1+1916C 〉 T, IVS1‐1154A 〉 G, and IVS11+1097G 〉 C) at various levels. An intronic SNP (IVS11+1097G 〉 C) with the highest significance of association ( p = 0.006) showed significant LD with four SNPs located around the first exon ( r 2 values 〉 0.18, D ′ 〉 0.5). A non‐synonymous coding SNP, D432E, showed a comparable level of correlation, but it was in a moderate LD only with IVS11+1097G 〉 C. The chromosomal dosage of one haplotype (T‐C‐C‐G‐T‐C in −39C 〉 T, IVS1+827C 〉 T, IVS1+1916C 〉 T, IVS1‐1154A 〉 G, D432E and IVS11+1097G 〉 C) estimated in each subject displayed significant correlation with adjusted radial BMD ( r = 0.15, p = 0.008; n = 331). Furthermore, multiple regression analyses revealed that the most significant correlation was achieved for the combination of IVS1+827C 〉 T and D432E ( r 2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Article
    DOI: 10.1359/jbmr.2003.18.9.1642
    RVK:
    XA 52230
    Language: English
    Publisher: Wiley
    Publication Date: 2003
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  • 7
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    Association of Multiple Nucleotide Variations in the Pituitary Glutaminyl Cyclase Gene ( QPCT ) With Low Radial BMD in Adult Women
    Wiley ; 2004
    In:  Journal of Bone and Mineral Research Vol. 19, No. 8 ( 2004-08), p. 1296-1301
    Details
    In: Journal of Bone and Mineral Research, Wiley, Vol. 19, No. 8 ( 2004-08), p. 1296-1301
    Abstract: Correlation between 13 genetic variations of the glutaminyl‐peptide cyclotransferase gene and adjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium, R54W showed a prominent association ( p = 0.0003), which was more striking when examined among 309 elder subjects (≥50 years; p = 0.0001). Contribution for postmenopausal bone loss was suggested. Introduction: Alterations in homeostatic regulation of estrogen through the hypothalamus‐pituitary‐gonadal axis (HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis‐susceptibility genes have been proposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin‐releasing hormone gene ( GnRH ). Here we report another example of genes: glutaminyl‐peptide cyclotransferase gene ( QPCT ), an essential modifier of pituitary peptide hormones, including GnRH. Materials and Methods: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locus with adjusted areal BMD (adj‐aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) was analyzed by haplotype estimation and calculation of D ′ and r 2 . Multiple regression analysis was applied for evaluating the combined effects of the variations. Results and Conclusions: LD analysis indicated strong linkage disequilibrium within the entire 30‐kb region of the QPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj‐aBMD, among which R54W (nt + 160C 〉 T) presented the most prominent association ( p = 0.0003). Striking association was observed for these SNPs among the 309 subjects 〉 50 years of age (R54W, p = 0.0001; −1095T 〉 C, p = 0.0002; −1844C 〉 T, p = 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might act in combination to determine the radial adj‐aBMD. These results indicate that genetic variations in QPCT are the important factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The data should provide new insight into the etiology of the disease and may suggest a new target to be considered during treatment.
    Type of Medium: Online Resource
    ISSN: 0884-0431 , 1523-4681
    URL: Article
    DOI: 10.1359/JBMR.040324
    RVK:
    XA 52230
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 2008867-X
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  • 8
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    S28. THE FEASIBILITY AND EFFICACY OF SOCIAL COGNITION AND INTERACTION TRAINING FOR OUTPATIENTS WITH SCHIZOPHRENIA IN JAPAN: A MULTICENTER RANDOMIZED CLINICAL TRIAL
    Oxford University Press (OUP) ; 2019
    In:  Schizophrenia Bulletin Vol. 45, No. Supplement_2 ( 2019-04-09), p. S316-S316
    Details
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 45, No. Supplement_2 ( 2019-04-09), p. S316-S316
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    URL: Article
    DOI: 10.1093/schbul/sbz020.573
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
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  • 9
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    Relationships between suppressor macrophages and macrophage precursors in the spleens from tumor-bearing mice
    Elsevier BV ; 1984
    In:  Cellular Immunology Vol. 85, No. 1 ( 1984-04), p. 45-57
    Details
    In: Cellular Immunology, Elsevier BV, Vol. 85, No. 1 ( 1984-04), p. 45-57
    Type of Medium: Online Resource
    ISSN: 0008-8749
    URL: Article
    DOI: 10.1016/0008-8749(84)90276-4
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1984
    detail.hit.zdb_id: 1462601-9
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  • 10
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    Hypermethylation of ASC/TMS1 Is a Sputum Marker for Late-Stage Lung Cancer
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 12 ( 2006-06-15), p. 6210-6218
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 12 ( 2006-06-15), p. 6210-6218
    Abstract: DNA hypermethylated gene promoter sequences are extremely promising cancer markers. Their use for risk assessment, early diagnosis, or prognosis depends on the timing of this gene change during tumor progression. We studied this for the proapoptotic gene ASC/TMS1 in lung cancer and used the findings to develop a sputum marker. ASC/TMS1 protein levels are reduced in all lung cancer types (30 of 40; 75%) but not in 10 preinvasive lesions. Hypermethylation of ASC/TMS1 is also associated with invasive cancers (41 of 152 or 27.0% of all lung cancer types) with variation in incidence between histopathologic types including 32.1% (26 of 81) of adenocarcinomas, 13.2% (7 of 53) of squamous cell carcinomas, 38.5% (5 of 13) of large-cell carcinomas, and 60% (3 of 5) of small-cell lung cancers. The hypermethylation is particularly correlated with late tumor stages being present in only 14% of stage I but 60% of later-stage tumors. The incidence of ASC/TMS1 hypermethylation in sputum DNA fully mimics the tissue findings being present in only 2% (2 of 85) of high-risk, cancer-free smokers, 15% (3 of 18) of patients with stage I non–small-cell lung cancer (NSCLC), but 41% of patients with stage III NSCLC (18 of 44), including 56% (10 of 18) of those with adenocarcinoma. Importantly, sputum is positive for this marker in 24% (10 of 42) of very high risk, clinically cancer-free individuals previously resected for stage I NSCLC. Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease. (Cancer Res 2006; 66(12): 6210-8)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-05-4447
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
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    detail.hit.zdb_id: 410466-3
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