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  • 1
    Online Resource
    Online Resource
    Acute myocardial necrosis during administration of amsacrine
    Wiley ; 1986
    In:  Cancer Vol. 57, No. 7 ( 1986-04), p. 1284-1286
    Details
    In: Cancer, Wiley, Vol. 57, No. 7 ( 1986-04), p. 1284-1286
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    URL: Article
    DOI: 10.1002/1097-0142(19860401)57:7〈〉1.0.CO;2-X
    DOI: 10.1002/1097-0142(19860401)57:7〈1284::AID-CNCR2820570705〉3.0.CO;2-#
    Language: English
    Publisher: Wiley
    Publication Date: 1986
    detail.hit.zdb_id: 1479932-7
    detail.hit.zdb_id: 2599218-1
    detail.hit.zdb_id: 2594979-2
    detail.hit.zdb_id: 1429-1
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  • 2
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    Online Resource
    A Meta-Analysis of Candidate Gene Polymorphisms and Ischemic Stroke in 6 Study Populations : Association of Lymphotoxin-Alpha in Nonhypertensive Patients
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Stroke Vol. 40, No. 3 ( 2009-03), p. 683-695
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 3 ( 2009-03), p. 683-695
    Abstract: Background and Purpose— Ischemic stroke is a multifactorial disease with a strong genetic component. Pathways, including lipid metabolism, systemic chronic inflammation, coagulation, blood pressure regulation, and cellular adhesion, have been implicated in stroke pathophysiology, and candidate gene polymorphisms in these pathways have been proposed as genetic risk factors. Methods— We genotyped 105 simple deletions and single nucleotide polymorphisms from 64 candidate genes in 3550 patients and 6560 control subjects from 6 case–control association studies conducted in the United States, Europe, and China. Genotyping was performed using the same immobilized probe typing system and meta-analyses were based on summary logistic regressions for each study. The primary analyses were fixed-effects meta-analyses adjusting for age and sex with additive, dominant, and recessive models of inheritance. Results— Although 7 polymorphisms showed a nominal additive association, none remained statistically significant after adjustment for multiple comparisons. In contrast, after stratification for hypertension, 2 lymphotoxin-alpha polymorphisms, which are in strong linkage disequilibrium, were significantly associated among nonhypertensive individuals: LTA 252A 〉 G (additive model; OR, 1.41 with 95% CI, 1.20 to 1.65; P =0.00002) and LTA 26Thr 〉 Asn (OR, 1.19 with 95% CI, 1.06 to 1.34; P =0.003). LTA 252A 〉 G remained significant after adjustment for multiple testing using either the false discovery rate or by permutation testing. The 2 single nucleotide polymorphisms showed no association in hypertensive subjects (eg, LTA 252A 〉 G, OR, 0.93; 95% CI, 0.84 to 1.03; P =0.17). Conclusions— These observations may indicate an important role of LTA-mediated inflammatory processes in the pathogenesis of ischemic stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.108.524587
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease
    Springer Science and Business Media LLC ; 2008
    In:  Nature Genetics Vol. 40, No. 5 ( 2008-5), p. 529-537
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 40, No. 5 ( 2008-5), p. 529-537
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/ng.129
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 4
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    Online Resource
    A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure
    Springer Science and Business Media LLC ; 2000
    In:  Journal of Molecular Medicine Vol. 78, No. 1 ( 2000-1), p. 36-46
    Details
    In: Journal of Molecular Medicine, Springer Science and Business Media LLC, Vol. 78, No. 1 ( 2000-1), p. 36-46
    Type of Medium: Online Resource
    ISSN: 0946-2716 , 1432-1440
    URL: Article
    DOI: 10.1007/s001090000079
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2000
    detail.hit.zdb_id: 1462132-0
    SSG: 12
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  • 5
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    Clinicians’ perspective on use of immune checkpoint inhibitors and related biomarkers for solid tumors.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e13643-e13643
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e13643-e13643
    Abstract: e13643 Background: Immune checkpoint inhibitors (ICIs) are a valuable treatment option for patients with malignant tumors, but only selected patients respond to ICIs. Available biomarkers are of limited use in guiding ICI therapy. We sought to examine clinicians’ perspective on the use of ICIs and biomarkers for treatment of malignant tumors and to identify unmet needs related to their use. Methods: We conducted in-depth telephone interviews of eight oncologists, and 100 oncologists completed online surveys. Results: Oncologists have a positive attitude toward use of ICIs, and 98% of them prescribe them in all approved indications. Clinicians report that only about half of the patients with solid tumors responded to treatment, overestimating the response rate to ICIs across most types of tumors they treat, compared with data in the literature. They ranked the lack of reliability of biomarkers to guide treatment (rating of 4.4 out of 7) as the top challenge with use of ICIs, followed by lack of overall efficacy and toxicity or occurrence of immune-related adverse events. The biomarkers most often used by survey participants were: a comprehensive panel including driver mutations and tumor mutational burden (69% of respondents), programmed cell death ligand-1 (PD-L1) expression (62%), and microsatellite instability (MSI) (56%). Oncologists indicated that they ordered biomarkers for each type of cancer according to their perceived usefulness of each biomarker in predicting the outcomes for ICI therapy, being more likely to use those perceived as useful or very useful. Conclusions: Clinicians indicate that more reliable therapy-response prediction biomarkers would have a great impact on treatment decisions for patients with solid tumors, reducing unnecessary treatments, side effects, and health care expenditures.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e13643
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Online Resource
    Identifying potential glycoproteomic biomarkers for diagnosis of colorectal cancer (CRC).
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e15529-e15529
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15529-e15529
    Abstract: e15529 Background: Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. Colorectal cancer (CRC) affects men and women of all racial and ethnic groups and is most often found in people who are 50 years old or older. To aid diagnosis and improve screening for CRC, this study focuses on identifying glycoprotein biomarkers using blood serum. Methods: Novel methods including liquid-chromatography/mass-spectrometry (LC-MS) with in-house peak integration software PB-Net were used to identify glycoprotein biomarkers by analyzing blood serum. Samples were sourced from different biorepositories including 245 CRC, 38 adenoma and 196 healthy controls. The data were split into 75% training and 25% hold-out test set for multivariable predictions. Statistical analysis was performed on normalized data to identify potential biomarkers differentiating adenoma and different stages of CRC samples from the healthy controls. Results: There were 419 significantly differentially expressed glycopeptides/peptides from comparisons between CRC and adenoma samples against the healthy control samples with an FDR 〈 0.05. A subset of these biomarkers were assessed, generating a 21-biomarker multivariable classifier model. We observed a test set AUC of 0.926, and the sensitivity for all stages of CRC was 90% (87% early stage, 92% late stage). Notably, sensitivity for adenomas was 79%, a large improvement upon the state of the art in adenoma diagnosis. Conclusions: Identification of these key glycopeptides/peptides in blood serum could prove to be a promising non-invasive diagnostic tool that can help improve screening and aid in early detection of advanced adenomas and CRC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e15529
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Online Resource
    Glycoproteomics as a powerful liquid biopsy-based predictor of checkpoint inhibitor treatment benefit in metastatic malignant melanoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 9545-9545
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9545-9545
    Abstract: 9545 Background: Protein glycosylation is the most abundant and complex form of post-translational protein modification. Glycosylation profoundly affects protein structure, conformation, and function. The elucidation of the potential role of differential protein glycosylation as biomarkers has so far been limited by the technical complexity of generating and interpreting this information. We have recently established a novel, powerful platform that combines liquid chromatography/mass spectrometry with a proprietary artificial-intelligence-based data processing engine that allows, for the first time highly scalable interrogation of the glycoproteome. Methods: Using this platform, we interrogated 526 glycopeptide (GP) signatures derived from 75 serum proteins in pretreatment blood samples from a cohort of 205 individuals (66 females, 139 males, age range 24 to 97 years) with metastatic malignant melanoma treated either with nivolumab plus ipilimumab (95 patients) or pembrolizumab (110 patients) immune-checkpoint inhibitor (ICI) therapy. Results: In an optimized assay containing 27 glycopeptides and 20 non-glycosylated peptides, we identified 14 GPs with abundance differences at FDR q≤0.05 with regard to PFS. Using 40% of the cohort as a training set and selecting 12 glycopeptide and non-glycosylated peptide biomarker features of the 47 total by LASSO shrinkage, we created a multivariable-model-based classifier for PFS that yielded a hazard ratio (HR) for prediction of likely ICI benefit of 7.5 at p 〈 0.0001. This classifier was validated in the test set comprised of the held-out 60% of patients, yielding a HR of 4.7 at a similar p-value for separating patients likely benefiting from ICI therapy and those likely not benefiting from ICI therapy (50% PFS of 18 months vs. 3 months based on classifier score above/below cutoff). This classifier has a sensitivity of 〉 99% to predict likely ICI benefit, while still performing at a specificity of 26%, thus helping to safely reduce ultimately unnecessary and non-beneficial exposure to these agents of one in four who otherwise would unnecessarily be exposed to them. Conclusions: Our results indicate that glycoproteomics holds a strong promise as a predictor for checkpoint inhibitor treatment benefit that appears to significantly outperform other currently pursued biomarker approaches in this context.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.9545
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Role of the α-, β-, and γ-Subunits of Epithelial Sodium Channel in a Model of Polygenic Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 1997
    In:  Hypertension Vol. 29, No. 1 ( 1997-01), p. 131-136
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 29, No. 1 ( 1997-01), p. 131-136
    Abstract: The pathophysiological basis of Liddle's syndrome, a rare autosomal dominant form of arterial hypertension, has been found to rest on missense mutations or truncations of the β- and γ-subunits of the epithelial sodium channel. The hypothesis has been advanced that molecular variants of these genes might also contribute to the common polygenic forms of hypertension. We tested this hypothesis by performing a cosegregation study in a reciprocal cross between the stroke-prone spontaneously hypertensive rat (SHRSP HD ) and a Wistar-Kyoto rat (WKY-1 HD ) reference strain. We carried out genetic mapping and chromosomal assignment of the α-, β-, and γ-subunits of the epithelial sodium channel using both linkage analysis and fluorescent in situ hybridization techniques. We demonstrate that in the rat, the β- and γ-subunits, as in humans, are in close linkage; they map to rat chromosome 1 and cosegregate with systolic pressure after dietary NaCl (logarithm of the odds [LOD] score, 3.7), although the peak LOD score of 5.0 for this quantitative trait locus was detected 4.4 cM away from the β-/γ-subunit locus. The α-subunit was mapped to chromosome 4 and exhibited no linkage to blood pressure phenotype. Comparative analysis of the complete coding sequences of all three subunits in the SHRSP HD and WKY-1 HD strains revealed no biologically relevant mutations. Furthermore, Northern blot comparison of mRNA levels for all three subunits in the kidney showed no differences between SHRSP HD and WKY-1 HD . Our results fail to support a material contribution of the epithelial sodium channel genes to blood pressure regulation in this model of polygenic hypertension.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/01.HYP.29.1.131
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1997
    detail.hit.zdb_id: 2094210-2
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  • 9
    Online Resource
    Online Resource
    Evidence for Association and Genetic Linkage of the Angiotensin-Converting Enzyme Locus With Hypertension and Blood Pressure in Men but Not Women in the Framingham Heart Study
    Ovid Technologies (Wolters Kluwer Health) ; 1998
    In:  Circulation Vol. 97, No. 18 ( 1998-05-12), p. 1766-1772
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 18 ( 1998-05-12), p. 1766-1772
    Abstract: Background —There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion ( ACE D/I ) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses. Methods and Results —The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (χ 2 P =.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively ( P =.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P =.03, multivariate-adjusted P =.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women. Conclusions —In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE , or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.97.18.1766
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1998
    detail.hit.zdb_id: 1466401-X
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  • 10
    Online Resource
    Online Resource
    Prospective Evaluation of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 1999
    In:  Circulation Vol. 99, No. 3 ( 1999-01-26), p. 340-343
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 3 ( 1999-01-26), p. 340-343
    Abstract: Background —The D/I polymorphism of the ACE gene has been studied in relation to a variety of cardiovascular disorders, including stroke. A number of small studies have been conducted, with inconsistent results. We investigated the association between ACE genotype and the incidence of stroke in a large, prospective, matched case-control sample from the Physicians’ Health Study. Methods and Results —In the Physicians’ Health Study, 348 subjects who had been apparently healthy at enrollment suffered a stroke during 12 years of follow-up, as determined from medical records and autopsy. A total of 348 cases were matched by age, time of randomization, and smoking habit to an equal number of controls (who had remained free of stroke). The D/I polymorphism was determined by polymerase chain reaction. Data were analyzed for the entire nested case-control sample, and also among a subgroup without a history of hypertension or diabetes mellitus, considered to be at low conventional risk (207 cases and 280 controls). All observed genotype frequencies were in Hardy-Weinberg equilibrium. The relative risk associated with the D allele was 1.11 (95% CI, 0.90 to 1.37; P =0.35), assuming an additive model in the matched analysis. Additional analyses assuming dominant or recessive effects of the D allele, as well as the analysis after stratification for low-risk status, showed no material as a statistically significant association. Conclusions —The results of this large, prospective study indicate that the ACE D/I gene polymorphism is not associated with subsequent risk of stroke.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.99.3.340
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1999
    detail.hit.zdb_id: 1466401-X
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