Search results for "Repair"
showing 10 items of 747 documents
Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of
2021
Simple Summary Genetic variability in transforming growth factor beta pathway (TGFB) has been reported to affect adverse events in radiotherapy. We investigated 40 germline polymorphisms in peripheral blood cells, covering the entire common genetic variability in the TGFβ1 ligand (gene TGFB1) and the TGFβ receptor-1 (TGFBR1) in 240 patients treated with primary radiotherapy for prostate cancer. Human lymphoblastoid cell lines (LCLs) were used to assess whether TGFB1 and TGFBR1 polymorphisms impact DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, for one polymorphism (rs10512263 in TGFBR1, C-variant allele, n = 35), a statistically signifi…
Abstract B63: Targeting cancer cells with a glucose-conjugated DNA repair inhibitor.
2011
Abstract Alkylating agents are important chemotherapeutic drugs used for the treatment of several types of cancers, including brain tumors, melanoma and lymphoma. These chemotherapeutic agents have a strong affinity towards oxygen atoms in DNA giving rise to the important genotoxic DNA lesions O6-methylguanine and O6-chloroethylguanine, which are responsible for the cytotoxic effects of several alkylating anticancer drugs (e.g. temozolomide and lomustine). The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is considered as an important player of drug resistance because it removes these DNA adducts from the DNA. The MGMT protein restores guanine in the DNA by a suicide repa…
Abstract 2679: Virtual screening of small molecule inhibitors towards the tumor suppressor p53 to overcome radioresistance of nasopharyngeal carcinom…
2010
Abstract The tumor suppressor p53 belongs to the most frequently mutated genes in cancer, including nasopharyngeal carcinoma (NPC). p53 is over-expressed in NPC, but the mutation rate is lower than in other tumor types. Therefore, it can be hypothesized that p53 might be involved in repair of DNA-damage after radiotherapy and causes recrudescence. Hence, the aim of the present investigation was to identify small molecule inhibitors for p53 to inhibit DNA repair after ionizing radiation of NPC. Approximately 260.000 2D-structures from NCI database were downloaded and different tautomers and charged stages between pH 5 and 9 were calculated for each compound. A total number of 906.587 drugs i…
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…
MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and …
2010
The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a key player in tumor cell resistance. Promoter methylation, MGMT activity and immunohistochemistry are used for determining the MGMT status. However, it is unclear whether MGMT promoter methylation correlates with MGMT activity and whether MGMT promoter methylation of the pretreatment tumor predicts the MGMT status of recurrences. To address these questions, we determined MGMT activity promoter methylation and immunoreactivity in pretreatment and recurrent glioblastomas (GB, WHO Grade IV), and in astrocytomas (WHO Grade III). We show that GB that were promoter methylated display a range of 0-62 fmol/mg MGMT and tumor…
Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools
2019
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…
Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength
2022
Lynch syndrome (LS) is an inherited genetic condition associated with increased predisposition to colorectal cancer (CRC) and other tumors and is caused by germline mutations in Mismatch Repair (MMR) or EPCAM genes. The identification of LS carriers is currently based on germline testing of subjects with MMR-deficient (dMMR) tumors or fulfilling clinical criteria, but the most efficient strategies to select patients who should be offered genetic testing are yet not well defined. In order to assess the most suitable selection mode to identify LS-related CRC patients, we retrospectively collected and analyzed all clinical and molecular information of 854 CRC patients, recruited from 2013 to 2…
FISH and CHIPs: Colorful Clues to Radiation-Induced Chromosomal Instability
2004
Radiation produces a variety of clonal and non-clonal chromosome aberrations that can be characterized by fluorescence in situ hybridization (FISH). Epigenetic changes affecting the expression of an essential DNA repair gene(s) may be an importantant mechanism for radiation-induced chromosomal instability. Expression profiling with specialized cDNA chips promises to identify candidate genes for the delayed effects of radiation and to provide new insights into the manifold and complex cellular responses to DNA damage. Much progress can be made by using FISH and CHIPs to study the mechanisms and biological consequences of ionizing radiation.
Boundary elements analysis of adhesively bonded piezoelectric active repair
2009
Abstract This paper presents the analysis of active piezoelectric patches for cracked structures by the boundary element method. A two-dimensional boundary integral formulation based on the multidomain technique is used to model cracks and to assemble the multi-layered piezoelectric patches to the host damaged structures. The fracture mechanics behavior of the repaired structures is analyzed for both perfect and imperfect interface between patches and host beams. The imperfect interface, representing the adhesive between two different layers, is modeled by using a “spring model” that involves linear relationships between the interface tractions, in normal and tangential directions, and the …
Collecting evidence for a stem cell hypothesis in HCC.
2010
Ever since Ernest McCulloch and James E Till defined essential stem cell properties, the field of stem cell biology has attracted increasing interest.1 Manipulating embryonic stem cells has resulted in advanced genetic technologies such as knock-out and transgenic animals, providing valuable models to study genetic influence on a wide variety of diseases.2 The success in manipulating stem cells and the ability to differentiate them into diverse tissues brought with them countless concepts of utilising stem cells in medicine. The idea of perpetually dividing pluripotent cells, capable of differentiating into nearly every possible cell or tissue type, seems like an inexhaustible resource for …