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Radiomics analysis for gynecologic cancers
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Such inter-site heterogeneity measures when combined with single site Haralick texture measures can better distinguish high-risk from low-risk patients. High-risk patients were defined as those with overall survival <60 months and with either amplification to the 19q12 involving cyclin E1 gene CCNE1 or incomplete surgical resection. Figure 19.1 shows the relative importance of features extracted using an elastic net regression classifier trained with leave-one-out cross-validation (LOOCV) (Figure 19.1a), the comparison in receiver operating curves (ROC) curves between classifiers trained with all features versus just the Haralick texture measures computed from the largest tumor site, and difference between the site entropy (SE) for the high- and low-risk patients (Figure 19.1c) and the difference in the most relevant texture measure, namely, entropy between those two groups of patients (Figure 19.1d). As seen, incorporating the disease heterogeneity across all the tumor sites helps to obtain a better differentiation of the patients. All Haralick textures were computed after rescaling the images to the range 0–255 and extracting textures from 128 bins using an offset distance of 1 pixel and averaging across all directions. A software wrapper in C++ using the Insight ToolKit software was used to generate the Haralick textures while the inter-site texture heterogeneity measures were computed using in-house software implemented in Matlab.
Gastric Cancer
Published in Dongyou Liu, Tumors and Cancers, 2017
Frequently found in the gastroesophageal junction/cardia and representing 50% of gastric cancer, tumors with CIN relate to intestinal type histology and often have copy number gains at 8q, 12q, 13q, 17q, and 20q and copy number losses at 3p, 4q, 5q, 15q, 16q, and 17q. In addition, CIN subtype shows amplifications of genes encoding receptor tyrosine kinases, EGFR, cell cycle genes cyclin E1 (CCNE1), cyclin D1 (CCND1), and cyclin-dependent kinase 6 (CDK6) [1,4,5].
Genetics of gastric cancer
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
Other infrequently observed alterations found in gastric cancer include the amplification of AKT-1, CYCLIN E1 (CCNE1), YES1, and ERBB1 (Nomura et al., 1986; Ochiai et al., 1997; Seki et al., 1985; Staal, 1987). Mutation analysis of p300 has found at least one gastric cancer case with a somatic mutation in the functionally important Cys/His region coupled with deletion of the second allele (Muraoka et al., 1996). Of note, p300 may be the target for deletions of chromosome 22q seen in gastric cancer. Interferon regulatory factor-1 (IRF1) also appears to be mutated in a small percentage of gastric cancers. Nozawa et al. identified a missense mutation in IRF1 in 1/9 gastric cancers. This mutation was accompanied by allelic loss of the second allele and decreased transcriptional activity from the mutant IRF1 (Nozawa et al., 1998). The role these alterations play in sporadic gastric cancer formation remains to be determined.
Cell cycle dysregulation on prenatal and postnatal arsenic exposure in skin of Wistar rat neonates
Published in Xenobiotica, 2023
Navneet Kumar, Astha Mathur, Suresh Kumar Bunker, Placheril J. John
There was a dose dependent decrease in transcript levels of cyclin A and cyclin B1 with increasing dose groups, whereas a similar increase in transcript levels of cyclin E1 with increasing dose groups. We also observed the downregulation of transcript levels of both CDK1 and CDK2 in a dose dependent manner. The increased expression of cyclin E1 has been shown to be involved in accelerated G1 to S phase transition (Resnitzky et al. 1994). The observed increase in cyclin E1 transcript expression levels can be a sign of increasing amount of cells transitioning to S phase. The cyclin A/CDK2 complex causes the transition of the cell cycle from the S phase to the G2 phase, and cyclin A then activates CDK1 to cause the cell to enter the M phase. The cyclin B/CDK1 complex maintains CDK1 activity during mitosis (Kalous et al. 2020). Disruption in the levels of CDK/cyclin complexes can result in cell cycle arrest in S phase and G2/M phase.
Advances in the treatment of platinum resistant epithelial ovarian cancer: an update on standard and experimental therapies
Published in Expert Opinion on Investigational Drugs, 2021
Shuk on Annie Leung, Panagiotis A. Konstantinopoulos
Table 4 highlights the key phase 2 studies, single-arm and multicenter randomized, of ATR/CHK1/WEE1 inhibitions in PROC. Leijen et al. assessed the combination of carboplatin and the WEE1 inhibitor, adavosertib, in patients with TP53-mutated platinum resistant or refractory ovarian cancer to and demonstrated an ORR of 43% [46]. Adavosertib was also tested alongside gemcitabine in a multi-center randomized phase 2 double-blind study among 124 patients with platinum resistant or refractory ovarian cancer. The median OS was 1.6 months longer in the adavosertib arm (4.6 vs. 3.0 months; 0 · 55, 95% CI 0 · 35–0 · 90, p = 0 · 015) [47]. Lee et al. assessed prexasertib, a checkpoint inhibitor, in high grade serous or endometrioid ovarian cancer and demonstrated an ORR of 33%, and of those, half (4/8) had tumors with cyclin E1 (CCNE1) overexpression [48].
Diagnosis and management of uterine serous carcinoma: current strategies and clinical challenges
Published in Expert Opinion on Orphan Drugs, 2020
Omar Najjar, Britt K. Erickson, Amanda N. Nickles-Fader
Significant advances have been made in characterizing the molecular landscape of USC through recent genome-wide analyses and single-nucleotide polymorphism (SNP) arrays. Mutations of HER2/neu, TP53, PIK3/AKT, and CCNE1/FBXW7 pathways have been described in multiple studies [47–50]. Sanger sequencing of 76 USC tumor samples found frequent mutations in TP53 (81.6%), PIK3CA (23.7%), FBXW7 (19.7%), and protein phosphatase 2 subunit alpha (PPP2R1A, 18.4%) [47]. Further analysis of a subset of 23 samples by SNP arrays found that 48% had gain-of-function mutations or amplification in PIK3CA, which encodes the catalytic subunit of phosphatidylinositol-3-kinase (PIK3). Moreover, 57% had alterations in CCNE1, which encodes cyclin E1, or FBXW7, which encodes a protein that targets cyclin E for ubiquitination. Zhao et al. performed whole-exome sequencing of 57 USC samples, 5 of which were excluded due to their very high mutational burden (>3000 somatic mutations) [48]. Among the remaining samples, frequent mutations were reported in well-characterized cancer genes (i.e., TP53, PIK3CA, PPP2R1A, FBXW7, CCNE1), as well as CHD4/Mi2b (19%), a member of the nucleosome remodeling and deacetylation complex, and TAF1 (13%), an element of transcription factor IID. Table 1 provides a summary of common genomic alterations that have been reported in USC.