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排序方式: 共有1139条查询结果,搜索用时 31 毫秒
951.
Peter H. J. Slootbeek Iris S. H. Kloots Minke Smits Inge M. van Oort Winald R. Gerritsen Jack A. Schalken Marjolijn J. L. Ligtenberg Katrien Grünberg Leonie I. Kroeze Haiko J. Bloemendal Niven Mehra 《British journal of cancer》2022,126(6):907
Background Molecular tumour boards (MTB) optimally match oncological therapies to patients with genetic aberrations. Prostate cancer (PCa) is underrepresented in these MTB discussions. This study describes the impact of routine genetic profiling and MTB referral on the outcome of PCa patients in a tertiary referral centre.Methods All PCa patients that received next-generation sequencing results and/or were discussed at an MTB between Jan 1, 2017 and Jan 1, 2020 were included. Genetically matched therapies (GMT) in clinical trials or compassionate use were linked to actionable alterations. Response to these agents was retrospectively evaluated.Results Out of the 277 genetically profiled PCa patients, 215 (78%) were discussed in at least one MTB meeting. A GMT was recommended to 102 patients (47%), of which 63 patients (62%) initiated the GMT. The most recommended therapies were PARP inhibitors (n = 74), programmed death-(ligand) 1 inhibitors (n = 21) and tyrosine kinase inhibitors (n = 19). Once started, 41.3% had a PFS of ≥6 months, 43.5% a PSA decline ≥50% and 38.5% an objective radiographic response.Conclusion Recommendation for a GMT is achieved in almost half of the patients with advanced prostate cancer, with GMT initiation leading to durable responses in over 40% of patients. These data justify routine referral of selected PCa patients to MTB’s.Subject terms: Prostate cancer, Cancer genetics, Targeted therapies, Cancer immunotherapy 相似文献
952.
Prediction of clinical benefit from androgen deprivation therapy in salivary duct carcinoma patients
Wim van Boxtel Gerald W. Verhaegh Ilse A. van Engen-van Grunsven Dianne van Strijp Leonie I. Kroeze Marjolein J. Ligtenberg Hans B. van Zon Yara Hendriksen Diederick Keizer Anja van de Stolpe Jack A. Schalken Carla M. van Herpen 《International journal of cancer. Journal international du cancer》2020,146(11):3196-3206
Androgen deprivation therapy (ADT) is first-line palliative treatment in androgen receptor-positive (AR+) salivary duct carcinoma (SDC), and response rates are 17.6–50.0%. We investigated potential primary ADT resistance mechanisms for their predictive value of clinical benefit from ADT in a cohort of recurrent/metastatic SDC patients receiving palliative ADT (n = 30). We examined mRNA expression of androgen receptor (AR), AR splice variant-7, intratumoral androgen synthesis enzyme-encoding genes AKR1C3, CYP17A1, SRD5A1 and SRD5A2, AR protein expression, ERBB2 (HER2) gene amplification and DNA mutations in driver genes. Furthermore, functional AR pathway activity was determined using a previously reported Bayesian model which infers pathway activity from AR target gene expression levels. SRD5A1 expression levels and AR pathway activity scores were significantly higher in patients with clinical benefit from ADT compared to those without benefit. Survival analysis showed a trend toward a longer median progression-free survival for patients with high SRD5A1 expression levels and high AR pathway activity scores. The AR pathway activity analysis, and not SRD5A1 expression, also showed a trend toward better disease-free survival in an independent cohort of locally advanced SDC patients receiving adjuvant ADT (n = 14) after surgical tumor resection, and in most cases a neck dissection (13/14 patients) and postoperative radiotherapy (13/14 patients). In conclusion, we are the first to describe that AR pathway activity may predict clinical benefit from ADT in SDC patients, but validation in a prospective study is needed. 相似文献
953.
954.
Christof Ulrich Leonie Kneser Roman Fiedler Julia Beckert Susann Wildgrube Eric Seibert Sylvia Fick Christoph Schfer Silke Markau Bogusz Trojanowicz Matthias Girndt 《Toxins》2021,13(12)
NLRP-3 inflammasome activation can result in interleukin-1β (IL-1β) release and inflammatory cell death (pyroptosis). Caspase-1 is able to trigger both processes. However, other caspases, caspase-4, -5 and -8, are believed to initiate pyroptosis without affecting IL-1 secretion. In this study, we evaluated two cardiovascular risk groups, haemodialysis patients (HD) and patients with intact kidney function but high blood pressure (BP), to analyse the mechanisms driving pyroptosis. Twenty HD were age-, gender- and diabetes-matched to BP. We found a common pyroptotic pattern in both patient groups, at which pyroptosis rates but not IL-1 β levels were significantly higher in monocytes (HD vs. BP: p < 0.05), granulocytes (p < 0.01) and lymphocytes (p < 0.01) of HD patients. As uremic toxins are drivers of inflammation and regulated cell death, we applied a monocyte- and macrophage-like THP-1 model system to demonstrate that the protein-bound uremic toxin indoxyl sulfate (IS) is an inducer of pyroptotic cell death, particularly engaging caspase-4/caspase-5 and to a lesser extent caspase-8 and caspase-1. These data suggest that the uremic toxin IS can mediate pyroptosis in HD patients and the inflammatory caspase-4 and/or caspase-5 contribute to pyroptosis rates to a higher extent in comparison to caspase-1. 相似文献
955.
956.
Richard Molenkamp Ewout Fanoy Leonie Derickx Theun de Groot Marcel Jonges Tjalling Leenstra Roel Nijhuis Suzan Pas Ali Vahidnia Christian von Wintersdorff Bert Mulder Marion Koopmans 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2021,26(40)
We evaluated routine testing with SARS-CoV-2 Delta variant-specific RT-PCR in regional hospital laboratories in addition to centralised national genomic surveillance in the Netherlands during June and July 2021. The increase of the Delta variant detected by RT-PCR correlated well with data from genomic surveillance and was available ca 2 weeks earlier. This rapid identification of the relative abundance and increase of SARS-CoV-2 variants of concern may have important benefits for implementation of local public health measures. 相似文献
957.
Nilima Dinesh Kumar Bram M. ter Ellen Ellen M. Bouma Berit Troost Denise P. I. van de Pol Heidi H. van der Ende-Metselaar Djoke van Gosliga Leonie Apperloo Orestes A. Carpaij Maarten van den Berge Martijn C. Nawijn Ymkje Stienstra Izabela A. Rodenhuis-Zybert Jolanda M. Smit 《Antimicrobial agents and chemotherapy》2022,66(1)
958.
Sultan S Heskin L Oaikhinan K Hynes N Akhter Y Courtney D 《Vascular and endovascular surgery》2005,39(2):183-190
Complications after open aortic surgery pose a challenge both to the vascular surgeon and the patient because of aging population, widespread use of cardiac revascularization, and improved survival after aortic surgery. The perioperative mortality rate for redo elective aortic surgery ranges from 5% to 29% and increases to 70-100% in emergency situation. Endovascular treatment of the postaortic open surgery (PAOS) patient has fewer complications and a lower mortality rate in comparison with redo open surgical repair. Two cases of ruptured abdominal aortic aneurysm (AAA) were managed with the conventional open surgical repair. Subsequently, spiral contrast computer tomography scans showed reperfusion of the AAA sac remnant mimicking a type III endoleak. These graft-related complications presented as vascular emergencies, and in both cases endovascular aneurysm repair (EVAR) procedure was performed successfully by aortouniiliac (AUI) stent graft and femorofemoral crossover bypass. These 2 patients add further merit to the cases reported in the English literature. This highlights the crucial importance of endovascular grafts in the management of such complex vascular problems. 相似文献
959.
960.