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1.
Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications. 相似文献
2.
Michels Guido Horn Rudolf Helfen Andreas Hagendorff Andreas Jung Christian Hoffmann Beatrice Jaspers Natalie Kinkel Horst Greim Clemens-Alexander Knebel Fabian Bauersachs Johann Busch Hans-Jörg Kiefl Daniel Spiel Alexander O. Marx Gernot Dietrich Christoph F. 《Der Anaesthesist》2022,71(4):307-310
Die Anaesthesiologie - 相似文献
3.
Wuteng Cao Huabin Hu Jiao Li Qianyu Wu Lishuo Shi Biao Li Jie Zhou Xinhua Wang Junhong Chen Chao Wang Huaiming Wang Weihao Deng Yan Huang Yanhong Deng 《International journal of cancer. Journal international du cancer》2023,153(11):1894-1903
Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy. 相似文献
4.
5.
Victoria L. Parker Matthew C. Winter John A. Tidy Barry W. Hancock Julia E. Palmer Naveed Sarwar Baljeet Kaur Katie McDonald Xianne Aguiar Kamaljit Singh Nick Unsworth Imran Jabbar Allan A. Pacey Robert F. Harrison Michael J. Seckl 《International journal of cancer. Journal international du cancer》2023,152(5):986-997
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus. 相似文献
6.
Lei Yang You-Ling Shi Yan Ma Wei-Wei Ren Guang-Ming Pang Jiao Liu 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2022,130(1):43-52
Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis. 相似文献
7.
Vilar-Compte Mireya Gaitán-Rossi Pablo Félix-Beltrán Lucía Bustamante Arturo V. 《Journal of immigrant and minority health / Center for Minority Public Health》2022,24(1):65-77
Journal of Immigrant and Minority Health - COVID-19 has disproportionally affected underrepresented minorities (URM) and low-income immigrants in the United States. The aim of the study is to... 相似文献
8.
9.
A Coupled FEM-BEM Approach for the Solution of the Free-Boundary Axi-Symmetric Plasma Equilibrium Problem
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M. Bonotto D. Abate P. Bettini & F. Villone 《Communications In Computational Physics》2022,31(1):27-59
In this paper we present a coupled Finite Element Method – Boundary Element Method (FEM-BEM) approach for the solution of the free-boundary axi-symmetric
plasma equilibrium problem. The proposed method, obtained from an improvement
of the Hagenow-Lackner coupling method, allows to efficiently model the equilibrium
problem in unbounded domains by discretizing only the plasma region; the external
conductors can be modelled either as 2D or 3D models, according to the problem of interest. The paper explores different iterative methods for the solution of the nonlinear
Grad-Shafranov equation, such as Picard, Newton-Raphson and Newton-Krylov, in order to provide a robust and reliable tool, able to handle large-scale problems (e.g. high
resolution equilibria). This method has been implemented in the FRIDA code (FRee-boundary Integro-Differential Axisimmetric – https://github.
om/matteobonotto/
FRIDA), together with a suitable Adaptive Integration Technique (AIT) for the computation of the source term. FRIDA has been successfully tested and validated against
experimental data from RFX-mod device, and numerical equilibria of an ITER-like device. 相似文献