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Jos B. Poell Leon J. Wils Arjen Brink Ralf Dietrich Christine Krieg Eunike Velleuer Ilkay Evren Elisabeth R. Brouns Jan G. de Visscher Elisabeth Bloemena Bauke Ylstra Ruud H. Brakenhoff 《International journal of cancer. Journal international du cancer》2023,152(2):227-238
Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient. 相似文献
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What is the Potential Interplay between Microbiome and Tumor Microenvironment in Oral Squamous Cell Carcinomas? 下载免费PDF全文
Chen-Xi Li Hui Liu Zhong-Cheng Gong 《Asian Pacific journal of cancer prevention》2022,23(7):2199-2213
Oral cancer, with an around 50% mortality rate, is one of the most common malignancies world-wide. It is often detected in advanced or terminal stage and has a poor prognosis, although substantial progress in cancer management. Microbiome has become an increasingly recognized factor that may contribute to the cancerous development. Oral microbiological population comprising more than 700 bacterial species, varies since saliva and different habitats of oral cavity. A shift of composition of oral microbiome from usual condition to functional inflammation to pathological state has been discovered amongst patients with premalignant disorders and oral carcinoma, with evidence suggesting the tumor microenvironment (TME) could strongly exacerbate the influence of oral microorganisms. The complex interactions taking place in either cancer formation or progression have been evaluated in several publications, however given their results’ heterogeneity, a review is needed to correctly untangle the potential correlation in this group of pro-carcinogenesis. In this review, we briefly summarize our current knowledge of the role of oral microbiome, focusing on its potential crosstalk with TME in oral squamous cell carcinomas (OSCC) more precisely, and pave the way for manipulating oral microbiome to deal with OSCC in the future. 相似文献
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Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is an emergent rare T cell non-Hodgkin lymphoma arising in association with a breast implant, particularly textured ones. Recent guidelines list cytopathological examination as the first essential step for diagnosis, routinely followed by CD30 immunohistochemistry (IHC) and flow cytometry (FC) for a T cell clone. The majority of BIA-ALCL literature regarding cytopathological evaluation describes morphology based on various preparation methods limited to cytospins and smears with the exception of at least one case report detailing cytomorphological and IHC findings on ThinPrep. This case report details initial diagnosis of BIA-ALCL rendered with CytoLyt prepared ThinPrep and cell block, including the specific antibodies used for IHC. The ThinPrep slide showed numerous singly dispersed large, atypical cells with abundant cytoplasm containing irregular nuclei with dispersed chromatin and prominent nucleoli in a background of macrophages, inflammatory cells and granular debris. TIA-1 and CD30 along with other T-cell markers, including specific antibodies, remains immunoreactive in tissue collected in CytoLyt solution. Cell size reduction, artifactual lymphoid cell aggregation and prominent nucleoli in benign and reactive conditions are among other ThinPrep cellular alterations pathologists should bear in mind. 相似文献
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The fractional uptake of ingested aluminium and aluminium compounds (aluminium citrate, aluminium nitrate, aluminium chloride, aluminium sulphate, aluminium hydroxide, aluminium oxide, aluminium metal, powdered aluminium pot electrolyte, acidic sodium aluminium phosphate (SALP), basic sodium aluminium phosphate (Kasal), sodium aluminium silicate and FD&C red 40 aluminium lake) from the gastro-intestinal tract of adult female rats was measured. This was determined by comparing retained body burden of 26Al at seven days post-admistration of an i.v. injection of 26Al-labelled aluminium citrate with that retained following the gastric admistration of 26Al-labelled test compounds as either solutions or suspended solid. The calculated percentage uptake of 26Al for all the aluminium solutions was similar: aluminium citrate 0.08%, aluminium chloride 0.05%, aluminium nitrate 0.05% and aluminium sulphate 0.21%. The uptake of 26Al administered as insoluble particulates was lower: 0.03% for aluminium hydroxide; 0.02% for aluminium oxide; 0.04% for powdered pot electrolyte; 0.12% for sodium aluminium silicate; and 0.09% for FD&C red 40 aluminium lake. For aluminium metal, SALP and Kasal the amount of 26Al present in the rats was insufficient to determine uptake and was less than 0.03%. The results produced for aluminium citrate, aluminium hydroxide and aluminium sulphate are close to those published for man. 相似文献
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Kazuko Sakai Takayuki Takahama Mototsugu Shimokawa Koichi Azuma Masayuki Takeda Terufumi Kato Haruko Daga Isamu Okamoto Hiroaki Akamatsu Shunsuke Teraoka Akira Ono Tatsuo Ohira Toshihide Yokoyama Nobuyuki Yamamoto Kazuhiko Nakagawa Kazuto Nishio 《Molecular oncology》2021,15(1):126
The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).
Abbreviations
- CIs
- confidence intervals
- ctDNA
- circulating tumor DNA
- ddPCR
- droplet digital PCR
- EGFR
- epidermal growth factor receptor
- MFs
- mutant fractions
- NGS
- next‐generation sequencing
- NSCLC
- non‐small cell lung cancer
- ORR
- overall response rate
- OS
- overall survival
- PD
- progressive disease
- PFS
- progression‐free survival
- PR
- partial response
- SD
- stable disease
- TKI
- tyrosine kinase inhibitor