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  • 1
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    Online Resource
    Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Abstract: It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II). METHODS: This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Patients with centralized evaluation of TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification of large-artery atherosclerosis, small-vessel occlusion, and stroke of undetermined cause were included. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. Cox proportional hazards models were used to assess the interaction of TOAST classification with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin. RESULTS: A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63–1.18]; P =0.34); 32 (3.6%) and 61 (7.0%) patients with small-vessel occlusion (hazard ratio, 0.51 [95% CI, 0.33–0.79]; P =0.002); and 68 (4.8%) and 87 (5.9%) patients with stroke of undetermined cause (hazard ratio, 0.80 [95% CI, 0.58–1.10]; P =0.17), with P =0.08 for the treatment×cause subtype interaction effect. There were no significant differences in severe or moderate bleeding events in patients with different cause and different treatment. CONCLUSIONS: In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.042233
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 2
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    Online Resource
    Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 16 ( 2020-06-01), p. 1774-1784
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 16 ( 2020-06-01), p. 1774-1784
    Abstract: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%] ) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%] ). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.19.02474
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Imaging Parameters Predict Recurrence After Transient Ischemic Attack or Minor Stroke Stratified by ABCD 2 Score
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 6 ( 2021-06), p. 2007-2015
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 6 ( 2021-06), p. 2007-2015
    Abstract: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD 2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD 2 score. Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD 2 score (low risk, 0–3; moderate risk, 4–5; and high risk, 6–7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD 2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200–2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042–1.687] ) but not in the high-risk group ( P 〉 0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.032424
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 4
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    Cardiac safety and efficacy for patients with early-stage breast cancer treated with pegylated liposomal doxorubicin (PLD) or doxorubicin.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 550-550
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 550-550
    Abstract: 550 Background: Anthracyclines play an important role in the treatment of breast cancer (BC) while cardiotoxicity, a serious side effect, limits the clinical application. Pegylated liposomal doxorubicin (PLD) is a new dosage form of doxorubicin encapsulated in liposomes, which can reduce the plasma free level of doxorubicin and drug to normal tissue delivery, thereby reducing cardiotoxicity. The aim of this study was to evaluate the cardiac safety and efficacy of PLD compared with doxorubicin as adjuvant therapy in breast cancer patients. Methods: This is an open-label, randomized trial involving patients with operable breast cancer who were at high risk of recurrence after radical sugery (NCT03949634). Patients were randomized (1:1) to receive adjuvant PLD or doxorubicin (A) and cyclophosphamide followed by taxanes ± trastuzumab. The primary endpoint was cardiotoxicity, which was defined as congestive heart failure (CHF) with clinical symptoms, or no symptoms but with an abnormal left ventricular ejection fraction (LVEF). Secondary endpoints included 5-year disease-free survival (DFS) rate, 5-year overall survival (OS) rate and safety. Results: Between November 2017 and September 2019, 247 patients were randomized and received study treatment (PLD arm, 131; A arm, 116). The median age was 49 years (range, 26-67) in PLD arm and 48 years (range, 25-70) in A arm. The pathological stages were 18.3% stage I, 58.0% stage II, and 22.1% stage III in PLD arm, while those of A arm were 20.7% stage I, 59.5% stage II, and 19.8% stage III. The median follow-up time was 43.0 months. The incidence of abnormal LVEF was 0 in the PLD arm and 1.7% the A arm (P = 0.220). The incidence of CHF was 0 in the PLD arm and 0.9% the A arm (P = 0.470). Survival data analysis is immature. The exploratory analysis of cardiac-related biomarkers showed that the incidence of high-sensitivity cardiac troponin-T (hs-cTnT) was lower in PLD arm than in A arm (3.8% vs. 30.2%, P 〈 0.001). Grade 3/4 adverse events (AEs) occurred in 42.7% patients in PLD arm and in 61.2% patients in A arm. The most common grade 3/4 AEs in PLD arm and A arm included neutropenia (34.4% vs. 55.2%), leukopenia (30.5% vs. 39.7%), and hand-foot syndrome (4.6% vs. 0.0%). Conclusions: Hs-cTnT elevation may have a role in the AE prediction of antharcycline. PLD usage may present lower incidence of cardiotoxicity than doxorubicin in the adjuvant treatment of patients with early-stage breast cancer. Clinical trial information: NCT03949634 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.550
    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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  • 5
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    Abstract GS1-08: Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple-negative breast cancer (cbcsg010): An open-label, randomised, multicentre, phase 3 trial
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. GS1-08-GS1-08
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. GS1-08-GS1-08
    Abstract: Background: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) comprises a taxane and an anthracycline. Concomitant capecitabine may add efficacy benefits, but robust data are lacking. The efficacy and safety of capecitabine integration into the TNBC adjuvant treatment regimen was evaluated. Methods: This was a randomised, open-label, phase 3 trial conducted in China (ClinicalTrials.gov identification NCT01642771). Post-resection, eligible female patients with early TNBC were randomly assigned (1:1) to either capecitabine treatment (3 cycles of capecitabine and docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine [TX-XEC]), or control treatment (3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil [T-FEC] ). Randomisation was centralised without stratification. The primary endpoint was 5-year disease-free survival (DFS). Findings: Between June 2012 and November 2013, 585 patients were randomized to treatment (capecitabine, n=297; control, n=288), of whom 561 were treated per protocol (n=288 and n=273, respectively). Median follow-up was 67 months. The 5-year DFS rate was longer with capecitabine than with control treatment (86·26% vs. 80·23%, hazard ratio 0·66, 95% confidence intervals 0·44-0·98; p=0·038). The 5-year overall survival rates were similar (93·27% vs. 90·55%, respectively). Overall, 38·89% patients had capecitabine dose reductions and 8·42% reported grade 3/4 hand-foot syndrome. The most common grade 3/4 hematologic toxicities were neutropenia (capecitabine 136 [45·79%] patients vs. control 119 [41·32%] patients) and febrile neutropenia (49 [16·5%] vs. 46 [15·97%] patients). Safety data were in line with the known capecitabine safety profile and generally comparable between arms. Interpretation: Capecitabine, when administered concomitantly with standard adjuvant taxane/anthracycline chemotherapy, significantly improved DFS rates in TNBC, with no new safety concerns. Table 1: Baseline patient demographics and clinical characteristics (PPS population; n=561)T-FEC (n=273)TX-XEC (n=288)pAge (years), mean ± SD48.30 ± 8.7649.07 ± 10.440·3501BSA (m2), mean ± SD1.60 ± 0.111.60 ± 0.110·4209Menstruation0·2946Premenopausal61·5757·09Postmenopausal38·4342·91Family History26·3726·830·9029Operation TypeBreast conserving21·8525·090·3683Mastectomy78·1574·91SLNB28·5226·130·5275Axillary dissection71·4873·87Node Stage0·5967N065·0665·97N123·7925·35N26·323·82N34·834·86T Stage0·2938T1a,b4·172·33T1c42·5041·25T250·4255·25T32·921·17Histology0·7190IDC89·6390·24ILC0·741·39Other9·638·36Grade0·2322I3·832·94II47·6640·76III48·5156·30Ki67 ≥30%+87·2185·770·6245LVI +14·8110·100·1363Surgery-to-chemo time (days), mean ± SD16·94 ± 7·7717·99 ± 9·240·1581Data are % except where specified.BSA=body surface area; IDC=invasive ductal carcinoma; ILC=invasive lobular carcinoma; LVI=lymphovascular invasion; PPS=per protocol set; SD=standard deviation;Table 2: Number of events (PPS population; n=561)T-FECTX-XEC(n=273)(n=288)Any event57 (20·88)41 (14·24)Second primary4 (1·47)5 (1·74)Contralateral breast5 (1·83)6 (2·08)Local recurrence18 (6·59)7 (2·43)Ipsilateral breast/Chest135Regional lymph nodes83Distant recurrence37 (13·55)29 (10·07)Liver37Lung1714Bone67Other2714Death26 (9·52)19 (6·60) Citation Format: Junjie Li, Keda Yu, Da Pang, Changqin Wang, Jun Jiang, Suisheng Yang, Yunjiang Liu, Peifen Fu, Yuan Sheng, Guojun Zhang, Yali Cao, Qi He, Shude Cui, Xijing Wang, Guosheng Ren, Xinzheng Li, Shiyou Yu, Pengxi Liu, Jinhai Tang, Ouchen Wang, Zhimin Fan, Guoqin Jiang, Jin Zhang, Zhimin Shao, Chinese Breast Cancer Study Group (CBCSG) 010. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple-negative breast cancer (cbcsg010): An open-label, randomised, multicentre, phase 3 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS1-08.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS19-GS1-08
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
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    Low concentration of metformin induces a p53-dependent senescence in hepatoma cells via activation of the AMPK pathway
    Spandidos Publications ; 2013
    In:  International Journal of Oncology Vol. 43, No. 5 ( 2013-11), p. 1503-1510
    Details
    In: International Journal of Oncology, Spandidos Publications, Vol. 43, No. 5 ( 2013-11), p. 1503-1510
    Type of Medium: Online Resource
    ISSN: 1019-6439 , 1791-2423
    URL: Article
    DOI: 10.3892/ijo.2013.2077
    RVK:
    XA 10000
    Language: English
    Publisher: Spandidos Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2079608-0
    detail.hit.zdb_id: 1154403-X
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  • 7
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    ENHANCED EXTERNAL COUNTERPULSATION REDUCES VASCULAR INFLAMMATION PROMOTED BY HYPERCHOLESTEROLEMIA
    Elsevier BV ; 2010
    In:  Journal of the American College of Cardiology Vol. 55, No. 10 ( 2010-03), p. A168.E1576-
    Details
    In: Journal of the American College of Cardiology, Elsevier BV, Vol. 55, No. 10 ( 2010-03), p. A168.E1576-
    Type of Medium: Online Resource
    ISSN: 0735-1097
    URL: Article
    DOI: 10.1016/S0735-1097(10)61577-X
    RVK:
    XA 17760
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 1468327-1
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  • 8
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    Efficacy of Clopidogrel-Aspirin Therapy for Stroke Does Not Exist in C YP2C19 Loss-of-Function Allele Noncarriers With Overweight/Obesity
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Stroke Vol. 51, No. 1 ( 2020-01), p. 224-231
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 1 ( 2020-01), p. 224-231
    Abstract: The role of dual-antiplatelet therapy with clopidogrel plus aspirin has been demonstrated to substantially decrease the risk of recurrent stroke among patients with minor stroke and transient ischemic attack. We aimed to determine whether the efficacy of clopidogrel-aspirin therapy among patients with minor stroke / transient ischemic attack was influenced by the stratification of CYP2C19 genotype and body mass index (BMI). Methods— CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with either LoFA of *2 or *3. Low/normal weight and overweight/obesity was defined as BMI 〈 25 and ≥25 kg/m 2 , respectively. Primary outcome was defined as stroke recurrence at 3 months. Results— In a total of 2933 patients, there were 1726 (58.8%) LoFA carriers and 1275 (43.5%) patients with overweight/obesity (BMI ≥25 kg/m 2 ). Stratified analyses by LoFA carrying status and BMI, hazard ratios (hazard ratios 95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.90 (0.60–1.36), 0.87 (0.56–1.35), 0.65 (0.39–1.09), and 0.40 (0.22–0.71) among subgroups of LoFA carriers with overweight/obesity, LoFA carriers with low/normal weight, LoFA noncarriers with overweight/obesity, and LoFA noncarriers with low/normal weight, respectively, with P =0.049 for interaction. Conclusions— Efficacy of clopidogrel-aspirin therapy in reducing the risk of stroke recurrence is not present in CYP2C19 LoFA noncarriers with overweight/obesity. Our study suggests that BMI significantly influences the correlation between CYP2C19 genotype and efficacy of clopidogrel-aspirin therapy. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00979589.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.119.026845
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 9
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    Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion
    Massachusetts Medical Society ; 2023
    In:  New England Journal of Medicine Vol. 388, No. 22 ( 2023-06-01), p. 2025-2036
    Details
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 388, No. 22 ( 2023-06-01), p. 2025-2036
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    URL: Article
    DOI: 10.1056/NEJMoa2214299
    RVK:
    XA 10000
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2023
    detail.hit.zdb_id: 1468837-2
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  • 10
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    TET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 22 ( 2017-11-15), p. 6069-6082
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 22 ( 2017-11-15), p. 6069-6082
    Abstract: DNA demethylases of the TET family function as tumor suppressors in various human cancers, but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here, we report that TET is transcriptionally upregulated in gastric cancer, where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a noncoding function of the 3′UTR, which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby led to EZH2 overexpression in gastric cancer. Our findings uncover a novel noncoding function for TET family proteins in facilitating gastric carcinogenesis. Cancer Res; 77(22); 6069–82. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-16-2964
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
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