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Frequently asked questions on surrogate endpoints in oncology-opportunities, pitfalls, and the way forward.
EClinicalMedicine
October 2024
Department of Oncology, Queen's University, Kingston, Canada.
Patients with cancer expect prolonged life (overall survival, OS) or better life (quality of life, QOL) from cancer treatments. However, majority of new cancer drugs are now being approved not based on improved OS or QOL, but based on surrogate endpoints such as tumor shrinkage or delayed tumor progression. These surrogate endpoints, including their validity as a proxy for overall survival, differ based on disease settings and lines of treatment but in general, most surrogate measures have weak correlation with outcomes that matter to patients.
View Article and Find Full Text PDFParatesticular/inguinal SMARCB1/INI1 deficient carcinomas with yolk sac tumour-like differentiation are aggressive somatic malignancies.
Histopathology
January 2025
Department of Diagnostic and Molecular Pathology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Aims: Extragonadal yolk sac tumour (YST) is rare, and may present a diagnostic challenge. YST differentiation was recently reported in some somatically derived tumours in the sinonasal location and in the female genital tract, together with a SMARCB1/INI1 loss. We report two paratesticular/inguinal tumours with striking morphological and immunohistochemical similarities with YST, further expanding the spectrum of extragonadal tumours with YST-like morphology and SMARCB1/INI1 loss.
View Article and Find Full Text PDFShedding light on the role of complement C4 activation in cancer.
Hum Immunol
December 2024
Department of Pharmaceutical and Biomedical Sciences College of Pharmacy, California Northstate University, 9700 West Taron Drive, Elk Grove, CA 95757, USA. Electronic address:
Complement C4 is a key component in the activation of classical and lectin complement pathways, which are observed in both animal tumor models and cancer patients. While its role in autoimmune disorders has been extensively studied, the functions of complement C4 and its activation in cancer have received inadequate consideration. Recent studies have detected C4 activation in animal tumor models and cancer patients, with its fragment C4d found in cancer tissues and lymph nodes.
View Article and Find Full Text PDFProgress, Pitfalls, and Impact of AI-Driven Clinical Trials.
Clin Pharmacol Ther
December 2024
Insilico Medicine US Inc, Cambridge, Massachusetts, USA.
Since the deep learning revolution of the early 2010s, significant efforts and billions of dollars have been invested in applying artificial intelligence (AI) to drug discovery and development (AIDD). However, despite high expectations, few AI-discovered or AI-designed drugs have entered human clinical trials, and none have achieved clinical approval. In this perspective, we examine the challenges impeding progress and highlight opportunities to harness AI's potential in transforming drug discovery and development.
View Article and Find Full Text PDFDiffusion tensor imaging along the perivascular space: the bias from crossing fibres.
Brain Commun
November 2024
Department of Clinical Sciences, Diagnostic Radiology, Medical Faculty, Lund University, 221 85 Lund, Sweden.
Non-invasive evaluation of glymphatic function has emerged as a crucial goal in neuroimaging, and diffusion tensor imaging along the perivascular space (DTI-ALPS) has emerged as a candidate method for this purpose. Reduced ALPS index has been suggested to indicate impaired glymphatic function. However, the potential impact of crossing fibres on the ALPS index has not been assessed, which was the aim of this cross-sectional study.
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