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  • 1
    Online Resource
    Online Resource
    Active case finding with case management: the key to tackling the COVID-19 pandemic
    Elsevier BV ; 2020
    In:  The Lancet Vol. 396, No. 10243 ( 2020-07), p. 63-70
    Details
    In: The Lancet, Elsevier BV, Vol. 396, No. 10243 ( 2020-07), p. 63-70
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(20)31278-2
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 2
    Online Resource
    Online Resource
    Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01)
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 3 ( 2023-01-20), p. 651-663
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 3 ( 2023-01-20), p. 651-663
    Abstract: The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P 〈 .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.22.00727
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  American Journal of Gastroenterology Vol. 118, No. 5 ( 2023-05), p. 802-811
    Details
    In: American Journal of Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. 5 ( 2023-05), p. 802-811
    Abstract: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P 〈 0.001) and participant-level AMR (10.9% vs 25.9%, P 〈 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P 〈 0.05), and a lower rate of shortening surveillance schedule ( P 〈 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.
    Type of Medium: Online Resource
    ISSN: 0002-9270 , 1572-0241
    URL: Article
    DOI: 10.14309/ajg.0000000000002055
    RVK:
    XA 18920
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 4
    Online Resource
    Online Resource
    Potential Clinical Significance of a Plasma-Based KRAS Mutation Analysis in Patients with Advanced Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2010
    In:  Clinical Cancer Research Vol. 16, No. 4 ( 2010-02-15), p. 1324-1330
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 16, No. 4 ( 2010-02-15), p. 1324-1330
    Abstract: Purpose: Non–small cell lung cancer (NSCLC) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC. Experimental Design: DNA extracted from plasma and matched tumor tissues were obtained from 273 patients with advanced stage NSCLC. Patients were followed up prospectively for treatment outcomes. KRAS mutations in codon 12 and 13 were detected using PCR-restriction fragment length polymorphism. Mutations in plasma and matched tumors were compared. Associations between KRAS mutation status and patients' clinical outcomes were analyzed. Results: KRAS mutation was found in 35 (12.8%) plasma samples and 30 (11.0%) matched tumor tissues. The consistency of KRAS mutations between plasma and tumors is 76.7% (23 of 30; κ = 0.668; P & lt; 0.001). Among 120 patients who received EGFR-TKI treatment, the response rate was only 5.3% (1 of 19) for patients with plasma KRAS mutation compared with 29.7% for patients with no KRAS mutation in plasma DNA (P = 0.024). The median progression-free survival time of patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for patients with wild-type KRAS (P & lt; 0.001). Conclusions: KRAS mutation in plasma DNA correlates with the mutation status in the matched tumor tissues of patients with NSCLC. Plasma KRAS mutation status is associated with a poor tumor response to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in selecting patients for such treatment. Clin Cancer Res; 16(4); 1324–30
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-09-2672
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 5
    Online Resource
    Online Resource
    Inferring the Evolution and Progression of Small-Cell Lung Cancer by Single-Cell Sequencing of Circulating Tumor Cells
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 16 ( 2019-08-15), p. 5049-5060
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 16 ( 2019-08-15), p. 5049-5060
    Abstract: Genomic analyses of small-cell lung cancer (SCLC) are limited by the availability of tumor specimens. This study aimed to investigate the suitability of single-cell sequencing of circulating tumor cells (CTC) as a method of inferring the evolution and progression of SCLCs. Experimental Design: Between July 1, 2011, and July 28, 2014, 48 consecutively diagnosed patients with SCLC were recruited for this study. CTCs were captured from each patient with CellSearch system. Somatic mutations and copy number alterations (CNA) were monitored by single-cell sequencing of CTCs during chemotherapy. Results: Single-cell sequencing of CTCs can provide a mutational atlas for SCLC. A 10-CNA score based on single CTCs was established as a classifier for outcomes of initial chemotherapy in patients with SCLC. The survival analyses demonstrated that patients with low CNA scores ( & lt;0) had significantly prolonged progression-free survival (PFS) and overall survival (OS) after first-line chemotherapy in comparison with those with high scores (≥0; PFS: 212 days vs. 110.5 days, P = 0.0042; and OS: 223.5 days vs. 424 days, P = 0.0006). The positive predictive value and negative predictive value of the CNA score for clinical subtype (refractory vs. sensitive) were 80.0% and 93.7%, respectively. By tracing allele-specific CNAs in CTCs isolated at different time points during chemotherapy, we showed that CNA heterogeneity might result from allelic losses of initially consistent CNAs. Conclusions: Single CTC-based sequencing can be utilized to depict the genomic profiles and evolutionary history of SCLC, thus offering the potential for clinical stratification of patients with SCLC.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-18-3571
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 6
    Online Resource
    Online Resource
    Cytoplasmic ERß expression to predict efficacy and survival of EGFR-TKI in EGFR-mutant NSCLC.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e19067-e19067
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19067-e19067
    Abstract: e19067 Background: Estrogen receptor pathway has been reported to be interacted with epidermal growth factor receptor (EGFR) signal pathway. This study focused on the impact of intracellular ERβ localization (cytoplasmic or nuclear) on efficacy of EGFR-TKI. Methods: Tumor tissue specimens from 149 stage IV NSCLC patients treated with EGFR-TKI were analyzed using immunohistochemistry (IHC) for ER expression (ERα or β) and their associations with clinicopathological variables and clinical outcomes. Significance of cyto-ERβ expression was further examined in NSCLC cell lines. Results: The expression of ERα and ERβ was detected in 15% and 28.9% of the patients, respectively. Cyto-ERβ positive cases showed shortened PFS compared with negative ones (3.1 months vs. 7.3 months, p=0.061). In the EGFR-mutant subgroup, differences of PFS were enlarged with significant statistics (4.7 months vs. 10.9 months, p=0.042). COX’s proportional hazard model showed that female, EGFR mutation and c-ERβ status were independent predictors for PFS. PC-9 cells present ERβ in cytoplasma and nucleus. Estrodial (E2) induced PC-9 cells moderately resistant to erlotinib with a 3-fold increase of IC50, and the resistance can be reversed by ER blocker (fulvestrant) or siRNA directed to ESR2. The E2 function was accomplished by nongenomic activation (MAPK phosphorylation) caused by E2 via cyto-ERβ. Combination treatment with erlotinib and fulvestrant turned out to be far more effective than either treatment alone in PC-9 cells. Conclusions: Cyto-ERβ expression may predict relatively poor efficacy to EGFR-TKI compared with non- cyto-ERβ expression in NSCLC patients harboring EGFR mutation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e19067
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Multiregion Sequencing Reveals the Genetic Heterogeneity and Evolutionary History of Osteosarcoma and Matched Pulmonary Metastases
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 1 ( 2019-01-01), p. 7-20
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 1 ( 2019-01-01), p. 7-20
    Abstract: Osteosarcoma is the most common primary bone malignancy, and the lung is the most frequent site of metastasis. The limited understanding of the tumoral heterogeneity and evolutionary process of genomic alterations in pulmonary metastatic osteosarcoma impedes development of novel therapeutic strategies. Here we systematically illustrate the genomic disparities between primary tumors and corresponding pulmonary metastatic tumors by multiregional whole-exome and whole-genome sequencing in 86 tumor regions from 10 patients with osteosarcoma. Metastatic tumors exhibited a significantly higher mutational burden and genomic instability compared with primary tumors, possibly due to accumulation of mutations caused by a greater number of alterations in DNA damage response genes in metastatic tumors. Integrated analysis of the architecture and relationships of subclones revealed a dynamic mutational process and diverse dissemination patterns of osteosarcoma during pulmonary metastasis (6/10 with linear and 4/10 with parallel evolutionary patterns). All patients demonstrated more significant intertumoral rather than intratumoral heterogeneity between primary tumors and metastatic tumors. Mutated genes were enriched in the PI3K–Akt pathway at both the early and late stages of tumor evolution and in the MAPK pathway at the metastatic stage. Conversely, metastatic tumors showed improved immunogenicity, including higher neoantigen load, elevated PD-L1 expression, and tumor-infiltrating lymphocytes than the corresponding primary tumors. Our study is the first to report the dynamic evolutionary process and temporospatial tumor heterogeneity of pulmonary metastatic osteosarcoma, providing new insights for diagnosis and potential therapeutic strategies for pulmonary metastasis. Significance: High-throughput sequencing of primary and metastatic osteosarcoma provides new insights into the diagnosis of and potential clinical therapeutic strategies for pulmonary metastasis.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-18-1086
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    Online Resource
    Online Resource
    Author Correction: Discovery of 42 genome-wide significant loci associated with dyslexia
    Springer Science and Business Media LLC ; 2023
    In:  Nature Genetics Vol. 55, No. 3 ( 2023-03), p. 520-520
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 55, No. 3 ( 2023-03), p. 520-520
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/s41588-023-01336-8
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    A novel algorithm to redefine blood-based tumor mutational burden for optimized prediction of clinical benefits from immunotherapy.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e20514-e20514
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e20514-e20514
    Abstract: e20514 Background: The previous reported predictive biomarker, blood-based tumor mutational burden (bTMB) can only predict progression-free survival (PFS) while failed to predict overall survival (OS) from atezolizumab over docetaxel, or to predict PFS or OS in the atezolizumab arm. Here we aimed to explore the underlying mechanism and develop an algorithm to redefine bTMB as a predictor of both PFS and OS from immunotherapy. Methods: Data from POPLAR (N = 211) and OAK (N = 642) trials was used for algorithm development in bTMB redefinition. The derived algorithm was validated in two independent NSCLC cohorts (cohort 1 N = 64; cohort 2 N = 184). Results: In POPLAR and OAK cohorts, bTMB-H was not associated with favorable OS (P = 0.68, HR 1.06; 95% CI, 0.81-1.38) from immunotherapy at the reported cut-point of 16, which was validated in our independent cohort 1 (P = 0.86, HR 0.39; 95% CI, 0.39-1.89). Further analysis showed that blood TMB was associated with maximum somatic allele frequency (Pearson r = 0.47 in POPLAR and OAK cohorts, Pearson r = 0.36 in the independent cohort 2), which was a negative prognostic factor and may impede the predictive value of bTMB. The bTMB was thus redefined (referred to as bTMB*) with mutations with allele frequency 〉 5% filtered out, when the correlation between bTMB and MSAF became less correlated (Pearson r = 0.09 and 0.07, respectively). Both better PFS and OS benefits from atezolizumab over docetaxel was observed in the redefined bTMB-H group as tested in POPLAR (PFS HR = 0.41, 95% CI, 0.21-0.80; OS HR = 0.34, 95% CI, 0.16-0.71) and validated in OAK (PFS HR = 0.49, 95% CI, 0.33-0.71; OS HR = 0.47, 95% CI, 0.29-0.77) with the cut-point of 12, while there was no significant association in redefined bTMB-L group (P interaction = 0.01 and 0.04 for PFS and OS in POPALR, 〈 0.001 and 0.06 for OAK PFS and OS in OAK). The results was further validated in our independent cohort 1 treated with anti-PD-1/PD-L1, where the redefined bTMB-H was also associated with favorable PFS compared with bTMB-L (Logrank P = 0.005, HR = 0.34, 95% CI, 0.26-0.75) and OS (Logrank P = 0.08, HR 0.35, 95% CI, 0.11-1.18). Conclusions: The allele frequency needs to be taken into consideration in the algorithm of bTMB. The redefined bTMB may serve as a predictor of both PFS and OS of immunotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e20514
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    Predicting significance of EGFR mutation existing in tissues and plasma concuurrently or alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) for advanced non-small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e19091-e19091
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19091-e19091
    Abstract: e19091 Background: To investigate predicting significance of EGFR mutations existing in tissues couples with plasma or either sample alone to EGFR–tyrosine kinase inhibitors (EGFR-TKIs) treatment for advanced non–small-cell lung cancer (A-NSCLC). Methods: Two hundred-eighty-seven A-NSCLC patients met following criteria were included into this study: 1) had received EGFR-TKIs as first- or second-line therapy; 2) had sufficient tissue and plasma samples for EGFR mutation analysis. All patients were divided into four subgroups which were wild-type EGFR in both of specimens (B - /T - ), mutated in both of specimens (B + /T + ), mutated only in one specimen (B + /T - and B - /T + ). EGFR mutation was screened by denaturing high performance liquid chromatograph (DHPLC) and confirmed by ARMS. Objective response rate (ORR) and progression-free survival (PFS) were compared among four subgroups. Results: Of all 287 patients, 101 patients carried EGFR mutation both in tissue and plasma, 103 patients carried mutation only in tissue (65 cases) or plasma (38 cases). Median PFS was 9.2 months (95% CI, 6.3 to 12.1) and 2.0 months (95% CI, 1.3 to 2.7) in B+/T+ and B-/T- group, respectively. For single mutated group, mPFS were 7.87 month for B-/T+ group (95% CI, 5.1 to 10.6) and 11.87 months for B+/T- group (95% CI, 3.3 to 20.5) (P=0.001). For ORR, 53.0% for B+/T+ group, 15.8% for B-/T- group, 40.0% for B-/T+ group and 28.9% for B+/T- group (P=0.000). EGFR-TKIs therapeutic line could not change trend which B+/T- or B+/T+ group had better PFS than B-/T+ group. Conclusions: Detection of EGFR mutation in tissue and plasma may have different significance in predicting response of EGFR-TKIs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e19091
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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