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  • Oxford University Press (OUP)  (5)
  • 1
    In: Genetics, Oxford University Press (OUP), Vol. 172, No. 4 ( 2006-04-01), p. 2309-2324
    Kurzfassung: Presenilin is the enzymatic component of γ-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for γ-tubulin in the pathway.
    Materialart: Online-Ressource
    ISSN: 1943-2631
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2006
    ZDB Id: 1477228-0
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 114, No. 10 ( 2022-10-06), p. 1371-1379
    Kurzfassung: Guidelines for follow-up after locoregional breast cancer treatment recommend imaging for distant metastases only in the presence of patient signs and/or symptoms. However, guidelines have not been updated to reflect advances in imaging, systemic therapy, or the understanding of biological subtype. We assessed the association between mode of distant recurrence detection and survival. Methods In this observational study, a stage-stratified random sample of women with stage II-III breast cancer in 2006-2007 and followed through 2016 was selected, including up to 10 women from each of 1217 Commission on Cancer facilities (n = 10 076). The explanatory variable was mode of recurrence detection (asymptomatic imaging vs signs and/or symptoms). The outcome was time from initial cancer diagnosis to death. Registrars abstracted scan type, intent (cancer-related vs not, asymptomatic surveillance vs not), and recurrence. Data were merged with each patient’s National Cancer Database record. Results Surveillance imaging detected 23.3% (284 of 1220) of distant recurrences (76.7%, 936 of 1220 by signs and/or symptoms). Based on propensity-weighted multivariable Cox proportional hazards models, patients with asymptomatic imaging compared with sign and/or symptom detected recurrences had a lower risk of death if estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative (triple negative; hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.54 to 0.99), or HER2 positive (HR = 0.51, 95% CI = 0.33 to 0.80). No association was observed for ER- or PR-positive, HER2-negative (HR = 1.14, 95% CI = 0.91 to 1.44) cancers. Conclusions Recurrence detection by asymptomatic imaging compared with signs and/or symptoms was associated with lower risk of death for triple-negative and HER2-positive, but not ER- or PR-positive, HER2-negative cancers. A randomized trial is warranted to evaluate imaging surveillance for metastases results in these subgroups.
    Materialart: Online-Ressource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 2992-0
    ZDB Id: 1465951-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 113, No. 3 ( 2021-03-01), p. 329-337
    Kurzfassung: We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
    Materialart: Online-Ressource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2992-0
    ZDB Id: 1465951-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), ( 2023-10-06)
    Kurzfassung: The impact of ongoing efforts to decrease opioid use on patients with cancer remains undefined. Our objective was to determine trends in new and additional opioid use in patients with and without cancer. Methods This is a retrospective cohort study using data from SEER-Medicare for opioid-naïve patients with solid tumor malignancies diagnosed from 2012 through 2017, and a random sample of patients without cancer. We identified 238,470 eligible patients with cancer and further focused on 4 clinical strata: patients without cancer, patients with metastatic cancer, patients with non-metastatic cancer treated with surgery alone (“surgery-alone”), and patients with non-metastatic cancer treated with surgery plus chemotherapy and/or radiotherapy (“surgery+”). We identified new, early additional, and long-term additional opioid use and calculated the change in predicted probability of these outcomes from 2012 to 2017. Results New opioid use was higher in patients with cancer (46.4%) than in those without (6.9%) (p  & lt; 0.001). From 2012 to 2017, the predicted probability of new opioid use was more stable in the cancer strata (relative declines: 0.1% surgery alone; 2.4% surgery+; 8.8% metastatic cancer), compared to the non-cancer stratum (20.0%) (p  & lt; 0.001 for each cancer to non-cancer comparison). Early additional use declined among surgery patients (-14.9% and -17.5% for surgery alone and surgery+, respectively), but was stable among metastatic patients (-2.8%, p=.50). Conclusions Opioid prescribing declined over time at a slower rate in patients with cancer than in patients without cancer. Our study suggests important but tempered effects of the changing opioid climate on patients with cancer.
    Materialart: Online-Ressource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 2992-0
    ZDB Id: 1465951-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: The Oncologist, Oxford University Press (OUP), Vol. 24, No. 2 ( 2019-02-01), p. 211-218
    Kurzfassung: Oncology clinicians often struggle with managing medications and vaccinations in older adults with cancer. We sought to demonstrate the feasibility and preliminary efficacy of integrating pharmacists into the care of older adults with cancer to enhance medication management and vaccination administration. Methods We randomly assigned patients aged ≥65 years with breast, gastrointestinal, or lung cancer receiving first-line chemotherapy to the pharmacy intervention or usual care. Patients assigned to the intervention met with a pharmacist once during their second or third chemotherapy infusion. We obtained information about patients' medications and vaccinations via patient report and from the electronic health record (EHR) at baseline and week 4. We determined the number of discrepant (difference between patient report and EHR) and potentially inappropriate (Beers Criteria assessed by nonintervention pharmacists blinded to group assignment) medications. We defined the intervention as feasible if & gt;75% of patients enrolled in the study and received the pharmacist visit. Results From January 17, 2017, to October 27, 2017, we enrolled and randomized 60 patients (80.1% of patients approached). Among those assigned to the intervention, 96.6% received the pharmacist visit. At week 4, intervention patients had higher rates of acquiring vaccinations for pneumonia (27.6% vs. 0.0%, p = .002) and influenza (27.6% vs. 0.0%, p = .002) compared with usual care. Intervention patients had fewer discrepant (5.82 vs. 8.07, p = .094) and potentially inappropriate (3.46 vs. 4.80, p = .069) medications at week 4, although differences were not significant. Conclusion Integrating pharmacists into the care of older adults with cancer is feasible with encouraging preliminary efficacy for enhancing medication management and improving vaccination rates. Implications for Practice Results of this study showed the feasibility, acceptability, and preliminary efficacy of an intervention integrating pharmacists into the care of older adults with cancer. Notably, patients assigned to the intervention had fewer discrepant medications and were more likely to acquire vaccinations for pneumonia and influenza. Importantly, this work represents the first randomized controlled trial involving the integration of pharmacists into the outpatient oncologic care of older adults with cancer. In the future, a larger randomized trial is needed to demonstrate the efficacy of this care model to enhance medication management and improve vaccination outcomes for older patients with cancer.
    Materialart: Online-Ressource
    ISSN: 1083-7159 , 1549-490X
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 2023829-0
    Standort Signatur Einschränkungen Verfügbarkeit
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