Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

Bukowski, Ronald

doi:10.1002/(sici)1096-911x(199902)32:2<124::aid-mpo10>3.0.co;2-z

Cited by 13 publications

(16 citation statements)

References 96 publications

(107 reference statements)

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“…In any case, the importance of these observations is related to the increased frequency of infusional doxorubicin usage in the clinic, especially during the treatment of both hematologic malignancies and solid tumors in the pediatric age group, as part of a strategy to decrease the potentially devastating long-term side effects of doxorubicin cardiac toxicity in the young. 44 …”

Section: Oxidative Base Modifications In Pbmc Dna During Infusional Dmentioning

confidence: 99%

Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin

Doroshow

Synold

Somlo

et al. 2001

Blood

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In prior studies, it was demonstrated that the redox metabolism of doxorubicin leads to the formation of promutagenic oxidized DNA bases in human chromatin, suggesting a potential mechanism for doxorubicin-related second malignancies. To determine whether a similar type of DNA damage is produced in the clinic, peripheral blood mononuclear cell DNA from 15 women treated with infusional doxorubicin (165 mg/m 2 ) as a single agent was examined for 14 modified bases by gas chromatography/mass spectrometry with selected ion monitoring. Prior to the 96-hour doxorubicin infusion, 13 different oxidized bases were present in all DNA samples examined. Chemotherapy, producing a steady-state level of 0.1 M doxorubicin, increased DNA base oxidation up to 4-fold compared to baseline values for 9 of the 13 bases studied. Maximal base oxidation was observed 72 to 96 hours after doxorubicin treatment was begun; the greatest significant increases were found for Thy Gly (4.2-fold), 5-OH-Hyd (2.5-fold), FapyAde (2.4-fold), and 5-OH-MeUra (2.4-fold). The level of the promutagenic base FapyGua increased 1.6-fold (P < .02), whereas no change in 8-OH-Gua levels was observed in peripheral blood mononuclear cell DNA during the doxorubicin infusion. These results suggest that DNA base damage similar to that produced by ionizing radia- IntroductionThe anthracycline antibiotic doxorubicin plays an important role in the treatment of a wide variety of hematologic malignancies as well as breast cancer and osteogenic sarcoma. 1 Although many competing hypotheses exist to explain the antineoplastic mechanism(s) of action of doxorubicin, there is little doubt that this drug interacts pleiotropically with DNA. 2 In addition to DNA interactions that may be important for the therapeutic effects of the drug, doxorubicin is a well-characterized mutagen. 3,4 When used clinically in combination with cyclophosphamide, doxorubicin is associated with a dramatically increased risk of second malignancy, particularly acute myelomonocytic leukemia. 5,6 However, the specific DNA lesions underlying the carcinogenic effect of doxorubicin remain to be elucidated. 7 Early investigations of the doxorubicin-DNA interaction characterized the ability of the planar anthracycline ring to intercalate into DNA 8 with more recent studies demonstrating a special affinity of the drug for dGdC-rich regions flanked by A:T base pairs. 9 Unfortunately, little evidence has been developed to demonstrate that intercalation of DNA by doxorubicin, per se, could explain the varied biochemical alterations (or mutagenicity) produced by this drug. 10 Furthermore, because of the intercalative function of the anthracycline ring, preclinical studies of the doxorubicin-DNA interaction initially focused on the ability of the anthracycline to inhibit DNA and RNA synthesis as well as specific DNA polymerases. 11-13 However, the doxorubicin concentrations required for inhibition of these enzymes were found to be in excess of those achievable clinically, which may explain the lack of correlation ...

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Section: Oxidative Base Modifications In Pbmc Dna During Infusional Dmentioning

confidence: 99%

Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin

Doroshow

Synold

Somlo

et al. 2001

Blood

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“…Survival rates for many patients with pediatric neoplasms have been steadily increasing during the past two decades due to significant improvements in existing treatment methods and new treatment approaches including intensive chemotherapy. Protecting patients from the adverse effects of intensive chemotherapy and radiation therapy has been a goal of clinical oncologists 1. Delayed and chronic toxicities are more problematic, since more than 80% of children and adolescents survive to adulthood.…”

Section: Introductionmentioning

confidence: 99%

Expression of stem cell pluripotency factors during regeneration in newts

Maki¹,

Suetsugu-Maki²,

Tarui³

et al. 2009

Developmental Dynamics

122

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In this study, we present data indicating that mammalian stem cell pluripotency-inducing factors are expressed during lens and limb regeneration in newts. The apparent expression even in intact tissues and the ensued regulation during regeneration raises the possibility that these factors might regulate tissuespecific reprogramming and regeneration. Furthermore, these factors should enable us to understand the similarities and differences between animal regeneration in the newt and stem cell strategies in mammals.

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“…Oral mucositis (or stomatitis) 19 is the inflammation of the oral mucosa, which arises as a common complication 20,21 in about 40% of chemotherapy and 80% of radiotherapy patients. 19 It results from the systemic effects of cytotoxic chemotherapeutic agents and from the local effects of radiation.…”

Section: Chemotherapy and Radiotherapymentioning

confidence: 99%

Importance of a dental approach in head and neck cancer therapy

Güneri

Çankaya

2005

Asia-Pac J Clncl Oncology

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Recent developments in molecular and genetic science have led to the early diagnosis of malignant cellular alterations of oral tissues, and escalated the number of new oral cancer cases detected each year. However, the treatment methods of cancer have not changed too much over the years, and the complications of surgery, chemotherapy and radiotherapy have continued to cause severe oral problems. Due to the increased frequency of this type of cancer in the population, dental practitioners have more opportunity to treat these patients. Therefore, dental health-care providers should continuously up-date their knowledge, not only about the oral cancer therapy and its oral complications, but also about its prevention and management options.

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Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

Cited by 13 publications

References 96 publications

Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin

Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin

Expression of stem cell pluripotency factors during regeneration in newts

Importance of a dental approach in head and neck cancer therapy

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