Search results for "mutation."

Phase 0/1 of Positron Emission Tomography (PET) imaging agent [18F]-ODS2004436 as a marker of EGFR mutation in patients with non-small cell lung canc…

2018

e24184Background: Multiple EGFR tyrosine kinase inhibitors (TKIs) are approved for treatment of NSCLC harboring EGFR activating mutations or secondary TKIs resistant mutation. We evaluate a new PET...

AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer.

2009

SummaryDysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth. Instead, these cells retain robust PDK1 activation and membrane localization and exhibit dependency on the PDK1 substrate SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PI…

Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T315I Bcr-Abl mutant by a redox-mediated me…

2010

Mutation of the Bcr–Abl oncoprotein is one of most frequent mechanisms by which chronic myelogenous leukemia (CML) cells become resistant to imatinib. Here, we show that treat- ment of cell lines harbouring wild type or mutant BCR–ABL with carboxyamidotriazole (CAI), a calcium influx and signal transduction inhibitor, inhibits cell growth, the expres- sion of Bcr–Abl and its downstream signalling, and induces apoptosis. Moreover, we show that CAI acts by increasing intracellular ROS. Clinically significant, CAI has also inhibitory effects on T315I Bcr–Abl mutant, a mutation that causes CML cells to become insensitive to imatinib and second generation abl kinase inhibitors.

Exome Sequencing to Predict Neoantigens in Melanoma

2015

Abstract The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to u…

No evidence of EMAST in whole genome sequencing data from 248 colorectal cancers.

2021

Microsatellite instability (MSI) is caused by defective DNA mismatch repair (MMR), and manifests as accumulation of small insertions and deletions (indels) in short tandem repeats of the genome. Another form of repeat instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), has been suggested to occur in 50% to 60% of colorectal cancer (CRC), of which approximately one quarter are accounted for by MSI. Unlike for MSI, the criteria for defining EMAST is not consensual. EMAST CRCs have been suggested to form a distinct subset of CRCs that has been linked to a higher tumor stage, chronic inflammation, and poor prognosis. EMAST CRCs not exhibiting MSI have b…

Familial breast cancer in Spain: A retrospective study of family history and clinical/pathologic characteristics from the GEICAM “El Álamo III” proje…

2013

e12513 Background: Family history (FH) of breast cancer (BC), ovarian cancer (OC), and individual features (IF), like early age of onset, bilateral BC, coexistence of BC and OC, and triple negative BC (TNBC) younger than 50 years, are suspicion criteria of hereditary BC. Although it is assumed in the literature that 15-30% of BC cases can be familial BC (FBC), only 5-10% of BC are hereditary, explained by a germline mutation in BRCA1 or 2. Moreover, there is no international consensus to define FBC (e.g. number of relatives affected, age of onset), in contrast with, e.g. Lynch syndrome and Amsterdam/Bethesda criteria, in order to offer genetic counseling. In Spain, there are not population…

Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer.

2022

Abstract Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 µm radius (to derive T cell p…

The Fitness Effects of Random Mutations in Single-Stranded DNA and RNA Bacteriophages

2009

Mutational fitness effects can be measured with relatively high accuracy in viruses due to their small genome size, which facilitates full-length sequencing and genetic manipulation. Previous work has shown that animal and plant RNA viruses are very sensitive to mutation. Here, we characterize mutational fitness effects in single-stranded (ss) DNA and ssRNA bacterial viruses. First, we performed a mutation-accumulation experiment in which we subjected three ssDNA (ΦX174, G4, F1) and three ssRNA phages (Qβ, MS2, and SP) to plaque-to-plaque transfers and chemical mutagenesis. Genome sequencing and growth assays indicated that the average fitness effect of the accumulated mutations was similar…

Human serum and erythrocytes protect white blood cells against DNA damage by ethylene oxide

1995

TCDD-dependent downregulation of gamma-catenin in rat liver epithelial cells (WB-F344).

2002

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is the most potent tumor promoter ever tested in rodents. Although it is known that most of the effects of TCDD are mediated by binding to the aryl hydrocarbon receptor (AHR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact-inhibition is a characteristic hallmark in tumorigenesis. In WB-F344 cells, TCDD induces a release from contact-inhibition manifested by a 2- to 3-fold increase in DNA-synthesis and the emergence of foci when TCDD (1 nM) is given to confluent cells. We focussed our interest on potential cell membrane proteins mediating contact-inhibition in WB-F344 cells, namely E-cadherin, alpha,- beta,-…