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1.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
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《Molecular therapy》2022,30(8):2856-2867
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3.
《Diagnostic Histopathology》2022,28(11):493-500
After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models. 相似文献
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Tengzhi Liu Kathrine Røe Redalen Morten Karlsen 《Journal of labelled compounds & radiopharmaceuticals》2022,65(7):191-202
Cyclotron-produced copper-64 radioisotope tracers offer the possibility to perform both diagnostic investigation by positron emission tomography (PET) and radiotherapy by a theranostic approach with bifunctional chelators. The versatile chemical properties of copper add to the importance of this isotope in medicinal investigation. [64Cu][Cu (ATSM)] has shown to be a viable candidate for imaging of tumor hypoxia; a critical tumor microenvironment characteristic that typically signifies tumor progression and resistance to chemo-radiotherapy. Various production and radiosynthesis methods of [64Cu][Cu (ATSM)] exist in labs, but usually involved non-standardized equipment with varying production qualities and may not be easily implemented in wider hospital settings. [64Cu][Cu (ATSM)] was synthesized on a modified GE TRACERlab FXN automated synthesis module. End-of-synthesis (EOS) molar activity of [64Cu][Cu (ATSM)] was 2.2–5.5 Ci/μmol (HPLC), 2.2–2.6 Ci/μmol (ATSM-titration), and 3.0–4.4 Ci/μmol (ICP-MS). Radiochemical purity was determined to be >99% based on radio-HPLC. The final product maintained radiochemical purity after 20 h. We demonstrated a simple and feasible process development and quality control protocols for automated cyclotron production and synthesis of [64Cu][Cu (ATSM)] based on commercially distributed standardized synthesis modules suitable for PET imaging and theranostic studies. 相似文献
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IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction. 相似文献
8.
For children with Developmental Coordination Disorder (DCD), the real-time coupling between frontal executive function and online motor control has not been explored despite reported deficits in each domain. The aim of the present study was to investigate how children with DCD enlist online control under task constraints that compel the need for inhibitory control. A total of 129 school children were sampled from mainstream primary schools. Forty-two children who met research criteria for DCD were compared with 87 typically developing controls on a modified double-jump reaching task. Children within each skill group were divided into three age bands: younger (6–7 years), mid-aged (8–9), and older (10–12). Online control was compared between groups as a function of trial type (non-jump, jump, anti-jump). Overall, results showed that while movement times were similar between skill groups under simple task constraints (non-jump), on perturbation (or jump) trials the DCD group were significantly slower than controls and corrected trajectories later. Critically, the DCD group was further disadvantaged by anti-jump trials where inhibitory control was required; however, this effect reduced with age. While coupling online control and executive systems is not well developed in younger and mid-aged children, there is evidence of age-appropriate coupling in older children. Longitudinal data are needed to clarify this intriguing finding. The theoretical and applied implications of these results are discussed. 相似文献
9.
《Surgical pathology clinics》2015,8(2):289-300
This article presents an overview of the curriculum deemed essential for trainees in pathology, with mapping to the Milestones competency statements. The means by which these competencies desired for pathology graduates, and ultimately practitioners, can best be achieved is discussed. The value of case (problem)-based learning in this realm, in particular the kind of integrative experience associated with hands-on projects, to both cement knowledge gained in the lecture hall or online and to expand competency is emphasized. 相似文献
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