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Cynthia S. E. Hendrikse MD Phyllis van der Ploeg MD PhD Nienke M. A. van de Kruis MD Jody H. C. Wilting MD Floor Oosterkamp BSc Pauline M. M. Theelen MSc Christianne A. R. Lok MD PhD Joanne A. de Hullu MD PhD Huberdina P. M. Smedts MD PhD M. Caroline Vos MD PhD Brenda M. Pijlman MD Loes F. S. Kooreman MD Johan Bulten MD PhD Marjolein H. F. M. Lentjes-Beer MD PhD Steven L. Bosch MD PhD Anja van de Stolpe MD PhD Sandrina Lambrechts MD PhD Ruud L. M. Bekkers MD PhD Jurgen M. J. Piek MD PhD 《Cancer》2023,129(9):1361-1371
Background
Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.Methods
Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.Results
Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.Conclusions
Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS. 相似文献2.
Nicole D. Facompre Pavithra Rajagopalan Varun Sahu Alexander T. Pearson Kathleen T. Montone Claire D. James Frederico O. Gleber-Netto Gregory S. Weinstein Jalal Jalaly Alexander Lin Anil K. Rustgi Hiroshi Nakagawa Joseph A. Califano Curtis R. Pickering Elizabeth A. White Bradford E. Windle Iain M. Morgan Roger B. Cohen Phyllis A. Gimotty Devraj Basu 《International journal of cancer. Journal international du cancer》2020,147(11):3236-3249
3.
Xin Zhang Tim Zegar Tim Weiser Feda H. Hamdan Benedict-Tilman Berger Romain Lucas Dimitrios-IIias Balourdas Swetlana Ladigan Phyllis F. Cheung Sven-Thorsten Liffers Marija Trajkovic-Arsic Bjoern Scheffler Andreas C. Joerger Stephan A. Hahn Steven A. Johnsen Stefan Knapp Jens T. Siveke 《International journal of cancer. Journal international du cancer》2020,147(10):2847-2861
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Sabra M. Abbott Roneil G. Malkani Phyllis C. Zee 《The European journal of neuroscience》2020,51(1):567-583
Circadian rhythm disorders have been classically associated with disorders of abnormal timing of the sleep–wake cycle, however circadian dysfunction can play a role in a wide range of pathology, ranging from the increased risk for cardiometabolic disease and malignancy in shift workers, prompting the need for a new field focused on the larger concept of circadian medicine. The relationship between circadian disruption and human health is bidirectional, with changes in circadian amplitude often preceding the classical symptoms of neurodegenerative disorders. As our understanding of the importance of circadian dysfunction in disease grows, we need to develop better clinical techniques for identifying circadian rhythms and also develop circadian based strategies for disease management. Overall this review highlights the need to bring the concept of time to all aspects of medicine, emphasizing circadian medicine as a prime example of both personalized and precision medicine. 相似文献
6.
Because STAT signaling is commonly activated in malignant gliomas as a result of constitutive EGFR activation, strategies for inhibiting the EGFR/JAK/STAT cascade are of significant interest. We, therefore, treated a panel of established glioma cell lines, including EGFR overexpressors, and primary cultures derived from patients diagnosed with glioblastoma with the JAK/STAT inhibitor cucurbitacin-I. Treatment with cucurbitacin-I depleted p-STAT3, p-STAT5, p-JAK1 and p-JAK2 levels, inhibited cell proliferation, and induced G2/M accumulation, DNA endoreduplication, and multipolar mitotic spindles. Longer exposure to cucurbitacin-I significantly reduced the number of viable cells and this decrease in viability was associated with cell death, as confirmed by an increase in the subG1 fraction. Our data also demonstrated that cucurbitacin-I strikingly downregulated Aurora kinase A, Aurora kinase B and survivin. We then searched for agents that exhibited a synergistic effect on cell death in combination with cucurbitacin-I. We found that cotreatment with cucurbitacin-I significantly increased Bcl-2/Bcl-xL family member antagonist ABT-737-induced cell death regardless of EGFR/PTEN/p53 status of malignant human glioma cell lines. Although >50% of the cucurbitacin-I plus ABT-737 treated cells were annexin V and propidium iodide positive, PARP cleavage or caspase activation was not observed. Pretreatment of z-VAD-fmk, a pan caspase inhibitor did not inhibit cell death, suggesting a caspase-independent mechanism of cell death. Genetic inhibition of Aurora kinase A or Aurora kinase B or survivin by RNA interference also sensitized glioma cells to ABT-737, suggesting a link between STAT activation and Aurora kinases in malignant gliomas. 相似文献
7.
Hannah Schwartz Jane McCusker Susan Law Phyllis Zelkowitz Jennifer Somera Santokh Singh 《Journal d'obstetrique et gynecologie du Canada》2021,43(3):322-328.e1
ObjectiveMental health problems affect up to 20% of women during pregnancy and the postpartum period. This study aimed to describe the mental health services and resources accessed by women with perinatal mental health problems (PMH) and to identify their unmet mental health care needs and preferences for support, as well as the barriers to accessing this support.MethodsParticipants were 18 years of age or older and spoke English or French. Consent was obtained 24 hours after delivery (T0) to screen for symptoms of depression and anxiety at 2 weeks postpartum (T1) using the Edinburgh Postnatal Depression Scale (EPDS) and the Generalized Anxiety Disorder Scale (GAD-7). Women with a positive screen (EPDS ≥10 or GAD-7 ≥10) were sent informational resources and were followed-up by telephone at 4 months postpartum (T2) to determine their use of these and other resources, their unmet needs, and their preferences for other resources or services.ResultsSeventy-three out of 344 participants (21.2%) screened positive, of whom 57 (78%) completed the T2 interview. Of those interviewed, 28% had used the informational resources provided by the study. Although 25% had consulted a health professional for mental health care, 37% had unmet mental health care needs. Preferences for additional support included web-based resources (30%), telephone support (28%), and booklets (25%). Lack of time (38%) and lack of childcare (23%) were the main barriers to seeking help.ConclusionsWeb- and telephone-based approaches have the potential to address the most common barriers to access support for women experiencing perinatal mental health problems. 相似文献
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9.
Measuring recall of medical information in non‐English‐speaking people with cancer: A methodology 下载免费PDF全文
10.
Analysis of stress distribution by endodontic posts 总被引:6,自引:0,他引:6