Identifying gene mutations in individual tumors is critical to improve the efficacy of cancer therapy by matching targeted drugs to specific mutations. Gastrointestinal stromal tumors (GIST) are stromal or mesenchymal subepithelial neoplasms affecting the gastrointestinal tract and frequently contain activating gene mutations in either KIT or platelet-derived growth factor A (PDGFRA). Although GIST is highly responsive to several selective tyrosine kinase inhibitors, combined use of inhibitors targeting other mutations is needed to further prolong survival in patients with GIST. In this study, we aim to screen and identify genetic mutations in GIST for targeted therapy using the new Ion Torrent next-generation sequencing platform. Utilizing the Ion Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes using DNA extracted from formalin-fixed and paraffin-embedded (FFPE) samples of 121 human gastrointestinal stromal tumors, set up stringent parameters for reliable variant calling by filtering out potential raw base calling errors, and identified frequent mutations in the KIT gene. This study demonstrates the utility of using Ion Torrent sequencing to efficiently identify human cancer mutations. This may provide a molecular basis for clinically developing new drugs targeting these gene mutations for GIST therapy.
Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.
Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5–10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.
Polyethylene-g-polystyrene (PE-g-PS) copolymers, which were prepared by the combination of the ROMP and ATRP method, were utilized to compatibilize LLDPE/PS blends. On one hand, the effect of PE-g-PS on the morphologies of LLDPE/PS blends was investigated. On the other hand, the influences of branch length and added amount of PE-g-PS on the cell morphology of foamed LLDPE/PS blends with different compositions were studied using supercritical CO 2 as a physical foaming agent in a batch foaming process. It was found that the presence of PE-g-PS in the LLDPE/PS blends showed different influences on the foaming behaviour, strongly depending on the composition of the blends (i.e. the weight ratio of LLDPE and PS). How the interplay of compatibilization and composition of the LLDPE/PS blends affected the foaming behaviour of the LLDPE/PS blends was studied. A reasonable explanation was ascribed to consecutive states of the interfacial region, resulting from different phase structures of the blends. Compared to pristine LLDPE and PS, the blends with a sea-island phase structure showed the improved foam morphology, but the presence of PE-g-PS did not strongly influence the foaming behaviours of these blends. In contrast, the presence of PE-g-PS dramatically promoted the foaming ability of LLDPE/PS blends with a co-continuous phase structure. It was ascribed to the strengthened interfacial adhesion blocking the channel between two components through which CO 2 was released, and the viscoelasticity of the blends was not the key factor to determine the foaming behaviour under the same foaming conditions in this work.
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