Analysis of repair of abasic sites in early onset breast cancer patients

Rossi, Ottavio; Carrozzino, Fabio; Cappelli, Enrico; Carli, Franca; Fròsina, Guido

doi:10.1002/(sici)1097-0215(20000101)85:1<21::aid-ijc4>3.0.co;2-t

Cited by 16 publications

(9 citation statements)

References 30 publications

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“…[16][17][18][19] Abasic sites, which are the result from the loss of a base in DNA, can occur by spontaneous hydrolysis with a relatively high frequency, enzymatically in the course of the repair of changed or abnormal bases as a result of chemotherapy, anti-tumor medications, radiation, and carcinogens. [20][21][22] Abasic site formation is noticeably increased during the repair of damaged nucleic bases.…”

Section: Cds Luminescence Titrations With Abasic Dnasupporting

confidence: 91%

<title>Inorganic nanoparticles as optical sensors of DNA</title>

et al. 2001

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The 1 -100 nanometer size range encompasses the dimensions of proteins and DNA. In this size range the bulk properties of inorganic materials become influenced by quantum mechanical effects and become size-dependent. Semiconductor nanoparticles are photoluminescent throughout the visible; the emission maximum is dictated by particle size, nature of the surface, and nature of the bulk material. We have used the photoluminescence of semiconductor nanoparticles to infer how oligonucleotides with unusual structure bind to the nanoparticles, providing insight into local structure and flexibility of the DNA. More recently we have examined the effects of base modifications on these binding events. Metallic nanoparticles can also interact with DNA, and these interactions can be monitored by the visible absorbance spectrum of the nanoparticles and by surface-enhanced Raman spectroscopy (SERS). Metallic surfaces that are rough on the nanometer scale are known to enhance the Raman signals of adsorbates by up to a million-fold. The result of photoluminescence titrations of abasic DNA and SERS DNA-nanoparticle studies will be reported.

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Section: Cds Luminescence Titrations With Abasic Dnasupporting

confidence: 91%

<title>Inorganic nanoparticles as optical sensors of DNA</title>

et al. 2001

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“…Normalizing activity to cell number affords a uniform basis for comparing tissues of different histology, avoiding potential problems attributable to tissue-and tumor-specific differences in the amount and composition of intracellular and extracellular proteins (e.g., ref. 25).…”

Section: Methodsmentioning

confidence: 99%

Apurinic/Apyrimidinic Endonuclease Activity Is Associated with Response to Radiation and Chemotherapy in Medulloblastoma and Primitive Neuroectodermal Tumors

Bobola

Finn

Ellenbogen

et al. 2005

Clinical Cancer Research

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Purpose: Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers resistance to radiation-and alkylator-induced cytotoxic abasic sites in human cells. We assayed apurinic/apyrimidinic endonuclease activity in medulloblastomas and primitive neuroectodermal tumors (PNET) to establish correlates with tumor and patient characteristics and with response to adjuvant radiation plus multiagent chemotherapy. Experimental Design: Ap endo activity was assayed in 52 medulloblastomas and 10 PNETs from patients 0.4 to 21years old. Ape1/Ref-1, the predominant human Ap endo activity, was measured in 42 medulloblastomas by immunostaining. Cox proportional hazards regression models were used to analyze the association of activity with time to tumor progression (TTP). Results: Tumor Ap endo activity varied 180-fold and was significantly associated with age and gender. Tumor Ape1/Ref-1was detected almost exclusively in nuclei. In a multivariate model, with Ap endo activity entered as a continuous variable, the hazard ratio for progression after adjuvant treatment in 46 medulloblastomas and four PNETs increased by a factor of 1.073 for every 0.01 unit increase in activity (P V 0.001) and was independent of age and gender. Suppressing Ap endo activity in a human medulloblastoma cell line significantly increased sensitivity to 1,3-bis(2-chlororethyl)-1-nitrosourea and temozolomide, suggesting that the association of tumor activity withTTP reflected, at least in part, abasic site repair. Conclusions: Our data (a) suggest that Ap endo activity promotes resistance to radiation plus chemotherapy in medulloblastomas/PNETs, (b) provide a potential marker of treatment outcome, and (c) suggest clinical use of Ap endo inhibitors to overcome resistance.

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“…As in hepatocellular carcinoma (HCC), a cytoplasmic localization of APE1 was associated with a significant lower degree of differentiation and with a shorter survival time, the localization of APE1 in liver biopsy is of prognostic value (22). Noteworthy, alteration in subcellular distribution of APE1 is not functionally related to the ability of cancerous tissue to repair abasic sites, suggesting that DNA repair by BER may not be affected (8,113,115). Therefore, it appears that the extranuclear roles of APE1 are responsible for its association with cancer.…”

Section: Clinical Perspectives: Altered Expression/distribution Of Apmentioning

confidence: 99%

The Many Functions of APE1/Ref-1: Not Only a DNA Repair Enzyme

Tell

Quadrifoglio

Tiribelli

et al. 2009

Antioxidants & Redox Signaling

440

412

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APE1/Ref-1 (APE1), the mammalian ortholog of Escherichia coli Xth, and a multifunctional protein possessing both DNA repair and transcriptional regulatory activities, has a pleiotropic role in controlling cellular response to oxidative stress. APE1 is the main apurinic/apyrimidinic endonuclease in eukaryotic cells, playing a central role in the DNA base excision repair pathway of all DNA lesions (uracil, alkylated and oxidized, and abasic sites), including single-strand breaks, and has also cotranscriptional activity by modulating genes expression directly regulated by either ubiquitous (i.e., AP-1, Egr-1, NF-B, p53, and HIF) and tissue specific (i.e., PEBP-2, Pax-5 and -8, and TTF-1) transcription factors. In addition, it controls the intracellular redox state by inhibiting the reactive oxygen species (ROS) production. At present, information is still inadequate regarding the molecular mechanisms responsible for the coordinated control of its several activities. Both expression and/or subcellular localization are altered in several metabolic and proliferative disorders such as in tumors and aging. Here, we have attempted to coalesce the most relevant information concerning APE1's different functions in order to shed new light and to focus current and future studies to fully understand this unique molecule that is acquiring more and more interest and translational relevance in the field of molecular medicine. Antioxid. Redox Signal. 11,[601][602][603][604][605][606][607][608][609][610][611][612][613][614][615][616][617][618][619]

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Analysis of repair of abasic sites in early onset breast cancer patients

Cited by 16 publications

References 30 publications

<title>Inorganic nanoparticles as optical sensors of DNA</title>

<title>Inorganic nanoparticles as optical sensors of DNA</title>

Apurinic/Apyrimidinic Endonuclease Activity Is Associated with Response to Radiation and Chemotherapy in Medulloblastoma and Primitive Neuroectodermal Tumors

The Many Functions of APE1/Ref-1: Not Only a DNA Repair Enzyme

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