Plasminogen activator in cultured Lewis lung carcinoma cells measured by chromogenic substrate assay.

A chromogenic substrate assay for the plasminogen activator (PA) activity of Lewis lung carcinoma cells has been developed. The cells were incubated with plasminogen, the activation of which to plasmin was measured by the amidolysis of the chromogenic substrate S-2251. This was routinely performed as a 4h serum-free assay, but a variation lasting 24 h, in medium supplemented with plasminogen-free inhibitor-reduced serum, produced similar results. The assay also detected PA released into the medium. PA activity was proportional to cell density, and the assay was non-toxic to the cells. Assays were performed on cultures derived from primary and metastatic tumours. Host cells were effectively eliminated from such cultures but, because of an initial phase of tumour-cell death, PA assays were not carried out until cultures became established. No consistent difference was detected between PA levels in primary and metastatic cultures. However, these cultures were shown to be atypical of the parent tumour; they grew slowly when reinjected at the primary site, and their metastatic potential was impaired

Mixed Supervision of Histopathology Improves Prostate Cancer Classification from MRI

Non-invasive prostate cancer detection from MRI has the potential to revolutionize patient care by providing early detection of clinically-significant disease (ISUP grade group >= 2), but has thus far shown limited positive predictive value. To address this, we present an MRI-based deep learning method for predicting clinically significant prostate cancer applicable to a patient population with subsequent ground truth biopsy results ranging from benign pathology to ISUP grade group~5. Specifically, we demonstrate that mixed supervision via diverse histopathological ground truth improves classification performance despite the cost of reduced concordance with image-based segmentation. That is, where prior approaches have utilized pathology results as ground truth derived from targeted biopsies and whole-mount prostatectomy to strongly supervise the localization of clinically significant cancer, our approach also utilizes weak supervision signals extracted from nontargeted systematic biopsies with regional localization to improve overall performance. Our key innovation is performing regression by distribution rather than simply by value, enabling use of additional pathology findings traditionally ignored by deep learning strategies. We evaluated our model on a dataset of 973 (testing n=160) multi-parametric prostate MRI exams collected at UCSF from 2015-2018 followed by MRI/ultrasound fusion (targeted) biopsy and systematic (nontargeted) biopsy of the prostate gland, demonstrating that deep networks trained with mixed supervision of histopathology can significantly exceed the performance of the Prostate Imaging-Reporting and Data System (PI-RADS) clinical standard for prostate MRI interpretation

PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex

PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signalling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42-dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN-deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42

Quality Comparison of 3 Tesla multiparametric MRI of the prostate using a flexible surface receiver coil versus conventional surface coil plus endorectal coil setup

Abstract: Purpose: To subjectively and quantitatively compare the quality of 3 Tesla magnetic resonance imaging of the prostate acquired with a novel flexible surface coil (FSC) and with a conventional endorectal coil (ERC). Methods: Six radiologists independently reviewed 200 pairs of axial, high-resolution T2-weighted and diffusion-weighted image data sets, each containing one examination acquired with the FSC and one with the ERC, respectively. Readers selected their preferred examination from each pair and assessed every single examination using six quality criteria on 4-point scales. Signal-to-noise ratios were measured and compared. Results: Two readers preferred FSC acquisition (36.5–45%) over ERC acquisition (13.5–15%) for both sequences combined, and four readers preferred ERC acquisition (41–46%). Analysis of pooled responses for both sequences from all readers shows no significant preference for FSC or ERC. Analysis of the individual sequences revealed a pooled preference for the FSC in T2WI (38.7% vs 17.8%) and for the ERC in DWI (50.9% vs 19.6%). Patients’ weight was the only weak predictor of a preference for the ERC acquisition (p = 0.04). SNR and CNR were significantly higher in the ERC acquisitions (p<0.001) except CNR differentiating tumor lesions from benign prostate (p=0.1). Conclusion: Although readers have strong individual preferences, comparable subjective image quality can be obtained for prostate MRI with an ERC and the novel FSC. ERC imaging might be particularly valuable for sequences with inherently lower SNR as DWI and larger patients whereas the FSC is generally preferred in T2WI. FSC imaging generates a lower SNR than with an ERC

Family and Medical Leave for Diagnostic Radiology, Interventional Radiology, and Radiation Oncology Residents in the United States: A Policy Opportunity

The American Board of Medical Specialties recently announced that effective July 1, 2021, member boards with training programs of 2 years or more must “establish requirements for candidates to become eligible for Initial Certification, including standards for training” and have “policies that accommodate reasonable leaves of absence from residency and fellowship training for personal or familial needs”. In preparation for this mandate, the American Board of Radiology (ABR) solicited comments from diverse stakeholders in March 2021—including the Association of Program Directors in Radiology, the Association of Program Directors in Interventional Radiology, and the ABR Initial Certification Advisory Committee for Radiation Oncology—with regards to Residency Service-Time Requirement, including considerations of family and medical leave. These communications included an initial proposed policy suggesting that “Programs may grant up to six weeks Parental, Caregiver and Medical Leave during the residency”. We appreciate the ABR\u27s efforts to seek feedback as it develops an updated policy. The purpose of this piece is to promote transparent discourse and to examine the nuanced issues pertaining to family and medical leave considerations within the broader context of Residency Service-Time Requirement policies for diagnostic radiology (DR), interventional radiology (IR), and radiation oncology (RO) residents, with the shared goal of optimizing both the training of competent clinicians worthy of public trust as well as professional well-being and diversity, equity, and inclusion. Given the rationale provided below, we recommend that the ABR leave policy allow a resident who is in good standing to take 12 weeks of family and medical leave during residency (in addition to 4 weeks of vacation per year), to sit for the Core/Qualifying Examinations on time, and to graduate without extension of training, with additional leave to be considered by the program director on a case-by-case basis