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21.
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22.
Md Maksudul Alam Janmaris Marin Fermin Patrick T. Spiller Chaning Burnett Xiaohua Rong Tara Moore-Medlin Caden O. Maxwell Alok R. Khandelwal Cherie-Ann O. Nathan 《Molecular carcinogenesis》2022,61(1):33-44
TP53 is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSCC). Patients with HPV-negative TP53 mutant HNSCC have the worst prognosis, necessitating additional agents for treatment. Since mutant p53 causes sustained activation of the PI3K/AKT/mTOR signaling pathway, we investigated the effect of rapalogs RAD001 and CCI-779 on HPV-negative mutTP53 HNSCC cell lines and xenografts. Rapalogs significantly reduced cell viability and colony formation. Interestingly, rapalogs-induced autophagy with no effect on apoptosis. Pretreatment with autophagy inhibitors, 3-methyladenine (3-MA) and ULK-101 rescued the cell viability by inhibiting rapalog-induced autophagy, suggesting that both RAD001 and CCI-779 induce non-apoptotic autophagy-dependent cell death (ADCD). Moreover, rapalogs upregulated the levels of ULK1 and pULK1 S555 with concomitant downregulation of the mTORC1 pathway. However, pretreatment of cells with rapalogs prevented the ULK-101-mediated inhibition of ULK1 to sustained autophagy, suggesting that rapalogs induce ADCD through the activation of ULK1. To further translate our in vitro studies, we investigated the effect of RAD001 in HPV-negative mutTP53 (HN31 and FaDu) tumor cell xenograft model in nude mice. Mice treated with RAD001 exhibited a significant tumor volume reduction without induction of apoptosis, and with a concomitant increase in autophagy. Further, treatment with RAD001 was associated with a considerable increase in pULK1 S555 and ULK1 levels through the inhibition of mTORC1. 3-MA reversed the effect of RAD001 on FaDu tumor growth suggesting that RAD001 promotes ACDC in HPV-negative mutTP53 xenograft. This is the first report demonstrating that rapalogs promote non-apoptotic ADCD in HPV-negative mutTP53 HNSCC via the ULK1 pathway. Further studies are required to establish the promising role of rapalogs in preventing the regrowth of HPV-negative mutTP53 HNSCC. 相似文献
23.
24.
Marie V. Plaisime PhD MPH Marie Jipguep-Akhtar PhD Joseph J. Locascio PhD Harolyn M. E. Belcher MD MHS Rachel R. Hardeman PhD MPH Katherine Picho-Kiroga PhD Sylvia P. Perry PhD Sean M. Phelan PhD MPH Michelle van Ryn PhD LMFT MPH John F. Dovidio PhD 《Health services research》2023,58(Z2):229-237
Objective
To examine the experience of interracial anxiety among health professionals and how it may affect the quality of their interactions with patients from racially marginalized populations. We explored the influence of prior interracial exposure—specifically through childhood neighborhoods, college student bodies, and friend groups—on interracial anxiety among medical students and residents. We also examined whether levels of interracial anxiety change from medical school through residency.Data Source
Web-based longitudinal survey data from the Medical Student Cognitive Habits and Growth Evaluation Study.Study Design
We used a retrospective longitudinal design with four observations for each trainee. The study population consisted of non-Black US medical trainees surveyed in their 1st and 4th years of medical school and 2nd and 3rd years of residency. Mixed effects longitudinal models were used to assess predictors of interracial anxiety and assess changes in interracial anxiety scores over time.Principal Findings
In total, 3155 non-Black medical trainees were followed for 7 years. Seventy-eight percent grew up in predominantly White neighborhoods. Living in predominantly White neighborhoods and having less racially diverse friends were associated with higher levels of interracial anxiety among medical trainees. Trainees' interracial anxiety scores did not substantially change over time; interracial anxiety was highest in the 1st year of medical school, lowest in the 4th year, and increased slightly during residency.Conclusions
Neighborhood and friend group composition had independent effects on interracial anxiety, indicating that premedical racial socialization may affect medical trainees' preparedness to interact effectively with diverse patient populations. Additionally, the lack of substantial change in interracial anxiety throughout medical training suggests the importance of providing curricular tools and structure (e.g., instituting interracial cooperative learning activities) to foster the development of healthy interracial relationships. 相似文献25.
Lucas F Soveral Gabriela G Korczaguin Pedro S Schmidt Isabel S Nunes Camilo Fernandes Carlos R Z rate-Blad s 《World journal of gastroenterology : WJG》2022,28(33):4762-4772
Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT. 相似文献
26.
27.
Greer Hunter R. Miller Kristen Samay Sadaf Nellan Anandani Green Adam L. 《Journal of neuro-oncology》2022,159(2):301-308
Journal of Neuro-Oncology - The role of white blood cells (WBC) in the pediatric central nervous system (CNS) tumor microenvironment is incompletely defined. We hypothesized that the WBC profile in... 相似文献
28.
von Heesen Maximilian Schuld Jochen Hollnder Sebastian Spiliotis Antonios E. Merscher Anna Scherber Philipp R. Igna Dorian Gbelein Gereon Glanemann Matthias 《European Surgery》2022,54(6):317-325
European Surgery - The beneficial outcomes of hepatectomy in patients with colorectal metastases have encouraged the attempts of repeated hepatectomy in patients with recurrent disease. Although... 相似文献
29.
Cornelius Anna Pilger Daniel Riechardt Aline Reitemeyer Emanuel Rübsam Anne Winterhalter Sibylle Maier Anna-Karina B. 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2022,260(3):957-965
Graefe's Archive for Clinical and Experimental Ophthalmology - To compare the blood flow situation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using optical... 相似文献
30.