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991.
992.
Yanjun Xu Xiaoling Tong Junrong Yan Xue Wu Yang W. Shao Yun Fan 《Translational oncology》2018,11(6):1364-1369
Non–small cell lung cancer (NSCLC) with activating EGFR mutations in exon 19 and 21 typically responds to EGFR tyrosine kinase inhibitors (TKI); however, for some patients, responses last only a few months. The underlying mechanisms of such short responses have not been fully elucidated. Here, we sequenced the genomes of 16 short-term responders (SR) that had progression-free survival (PFS) of less than 6 months on the first-generation EGFR TKI and compared them to 12 long-term responders (LR) that had more than 24 months of PFS. All patients were diagnosed with advanced lung adenocarcinoma and harbored EGFR 19del or L858R mutations before treatment. Paired tumor samples collected before treatment and after relapse (or at the last follow-up) were subjected to targeted next-generation sequencing of 416 cancer-related genes. SR patients were significantly younger than LR patients (P < .001). Collectively, 88% of SR patients had TP53 variations compared to 13% of LR patients (P < .001). Additionally, 37.5% of SR patients carried EGFR amplifications compared to 8% of LR patients. Other potential primary resistance factors were also identified in the pretreatment samples of 12 SR patients (75%), including PTEN loss; BIM deletion polymorphism; and amplifications of EGFR, ERBB2, MET, HRAS, and AKT2. Comparatively, only three LR patients (25%) were detected with EGFR or AKT1 amplifications that could possibly exert resistance. The diverse preexisting resistance mechanisms in SR patients revealed the complexity of defining treatment strategies even for EGFR-sensitive mutations. 相似文献
993.
Xinbo Xu Heng Liu Neil Gross Dongmin Wei Ye Qian Wenming Li Peng Wei Guojun Li Fenghua Zhang Zheng Yang Dapeng Lei Xinliang Pan 《Translational oncology》2018,11(5):1244-1250
Hypopharyngeal cancer (HC) is the most common subset of head and neck cancers. These tumors often have an aggressive clinical outcome characterized by local invasion and regional nodal metastasis. Upregulated miRNAs might be useful as biomarkers for prognosis and molecular targets for these tumors. We determined tumor expression of candidate miRNAs using microarray in 8 HC patients and validated in 372 HC patients. We also used paired tumorous and mucosal tissue to verify the miRNA expression. Log-rank test and Cox model were used to evaluate the survival; and Harrell's C-index was used to compare concordance of Cox models. Our results indicated 7 miRNAs aberrantly expressed in HC. Three of these candidate miRNAs (miRNA-4415, miRNA-200a, and miRNA-30b) were selected for further qRT-PCR validation and all of them were frequently found upregulated in HC tumors; with miR-4451 being the most differentially expressed. Moreover, high expression of miR-4451 was positively correlated with advanced tumor stage and increased mortality risk (HR: 1.6, 95% CI: 1.2–2.3; adjusted HR: 1.5, adjusted 95% CI: 1.1–2.1). Finally, significantly higher expression of miR-4451 in tumors compared to in fresh adjacent normal tissues indicates an oncogenic role of miR-4451 in this tumor. Upregulated miR-4451 in HC samples were frequently found and is significantly associated with advanced stage and poor survival of HC, which may indicate an association of this miRNA with the carcinogenesis process in this tumor site; and they could serve as a prognostic biomarker as well as help develop potential new targets for therapy. 相似文献
994.
Zehang Jiang Zhixian Liu Mengyuan Li Cai Chen Xiaosheng Wang 《Translational oncology》2018,11(5):1171-1187
Although immunotherapy continues to demonstrate efficacy in a variety of refractory cancers, currently, no any immunotherapeutic strategy is clinically used for gastric cancer (GC) except its microsatellite instable subtype. Thus, it is important to identify molecular biomarkers for predicting the responders to GC immunotherapy. TP53 mutations frequently occur in GC and are associated with unfavorable clinical outcomes in GC. We performed a comprehensive characterization of the associations between TP53 mutations and immune activities in GC based on two large-scale GC cancer genomics data. We compared expression and enrichment levels of 787 immune-related genes and 23 immune gene-sets among TP53-mutated GCs, TP53‐wildtype GCs, and normal tissue, and explored the correlations between p53-mediated pathways and immune activities in GC. Strikingly, almost all analyzed immune gene-sets were significantly downregulated in enrichment levels in TP53-mutated GCs compared to TP53‐wildtype GCs. These less active immune pathways and cell types in TP53-mutated GCs included 15 immune cell types and function, tumor-infiltrating lymphocytes, regulatory T cells, immune checkpoint, cytokine and cytokine receptor, human leukocyte antigen, pro‐inflammatory, and parainflammation. Moreover, we identified a number of p53-mediated pathways and proteins that were significantly associated with immune activities in GC. Furthermore, we demonstrated that the TP53 mutation itself could result in the depressed immune activities in GC and other cancer types. We revealed that chromosomal instability was an important mechanism for the depressed tumor immunity in TP53-mutated cancers. Finally, we showed that immune cell infiltration and immune activities were likely positively associated with survival prognosis in GC. Our findings suggest that p53 may play an important role in activating tumor immunity in GC and other cancer types and that the TP53 mutation status could be useful in stratifying cancer patients responsive to a certain immunotherapy. 相似文献
995.
996.
Yuanyuan Wang Shanghui Guan Yanhong Bi Sixiang Lin Jianjun Ma Qian Xing Chonghua Liu Rui Zhang Zhen Qu Peng Jiang Xue Chen Yufeng Cheng 《Translational oncology》2018,11(6):1358-1363
The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards models were performed for both PFS and OS for all assumed predictor variables. Statistically significant predictor variables (P < .05) on univariate analysis were then included in multivariate Cox proportional-hazards models, which were performed to compare the effects of RT delay on PFS and OS. A total of 316 patients were finally enrolled in this prospectively multicentric study. Time to RT after surgery varied from 12 days to over 60 days (median, 26 days). Multivariate analysis showed that delay to RT longer than the median does not appear to be a survival cost. There was also no statistically difference in PFS (P = .513) or OS (P = .236) between patients stratified by quartiles (≤21 days vs ≧35 days). However, patients with particularly long delays (≧42 days) demonstrated a detrimental impact on OS (P = .021) but not PFS (P = .580). Delaying postoperative RT of esophageal cancer does not impact PFS, but results in a significant reduction on OS if delaying longer than 6 weeks. 相似文献
997.
Theropod footprints from the Jingshang tracksite in the Lower Cretaceous Dabeigou Formation of the Luanping Basin, Hebei Province, China, are re-evaluated after new discoveries at this locality. They occur in a succession with sandstone, mudstone, and calcareous shale. The depositional environment was a shallow lake shore, comparable in age to the famous Jehol Biota. Based on the distinct morphology with peculiar features of the ratio of the outer digits, the footprints formerly assigned to Changpeipus carbonicus are now referred to the new ichnogenus and combination Lockleypus luanpingensis. The possible trackmaker was a relatively large ornithomimosaurian theropod thus far not known from the skeletal record of the Jehol Biota. 相似文献
998.
Contrasting genetic metrics and patterns among naturalized rainbow trout (Oncorhynchus mykiss) in two Patagonian lakes differentially impacted by trout aquaculture 下载免费PDF全文
Lisa W. Seeb James E. Seeb María I. Cádiz Selim S. Musleh Ivan Arismendi Gonzalo Gajardo Ricardo Galleguillos Daniel Gomez‐Uchida 《Ecology and evolution》2018,8(1):273-285
Different pathways of propagation and dispersal of non‐native species into new environments may have contrasting demographic and genetic impacts on established populations. Repeated introductions of rainbow trout (Oncorhynchus mykiss) to Chile in South America, initially through stocking and later through aquaculture escapes, provide a unique setting to contrast these two pathways. Using a panel of single nucleotide polymorphisms, we found contrasting genetic metrics and patterns among naturalized trout in Lake Llanquihue, Chile's largest producer of salmonid smolts for nearly 50 years, and Lake Todos Los Santos (TLS), a reference lake where aquaculture has been prohibited by law. Trout from Lake Llanquihue showed higher genetic diversity, weaker genetic structure, and larger estimates for the effective number of breeders (Nb) than trout from Lake TLS. Trout from Lake TLS were divergent from Lake Llanquihue and showed marked genetic structure and a significant isolation‐by‐distance pattern consistent with secondary contact between documented and undocumented stocking events in opposite shores of the lake. Multiple factors, including differences in propagule pressure, origin of donor populations, lake geomorphology, habitat quality or quantity, and life history, may help explain contrasting genetic metrics and patterns for trout between lakes. We contend that high propagule pressure from aquaculture may not only increase genetic diversity and Nb via demographic effects and admixture, but also may impact the evolution of genetic structure and increase gene flow, consistent with findings from artificially propagated salmonid populations in their native and naturalized ranges. 相似文献
999.
1000.